City of Hope, known for its robust integration of advanced scientific discovery and clinical application, has demonstrated a compelling commitment to pushing the frontiers of cancer care. At this year’s ASCO meeting, their contributions signal a pivotal evolution towards treatment paradigms that emphasize precision medicine — tailoring therapy based on individual genetic, molecular, and immunological profiles. The center’s physician-scientists are not only presenting data but will also lead critical sessions, panel discussions, and educational symposia, underscoring their leadership within the global oncology community.

Among the highlights is the phase 3 SUNMO trial, which investigates the efficacy and safety of mosunetuzumab combined with polatuzumab vedotin (Mosun-Pola) compared with the established rituximab, gemcitabine, and oxaliplatin regimen (R-GemOx) in relapsed/refractory large B-cell lymphoma (LBCL). The updated data dissect outcomes in second-line versus later-line treatment settings, providing nuanced insights that could influence clinical decision-making in lymphoma subtypes resistant to previous therapies. These findings stress the importance of bispecific antibodies and antibody-drug conjugates in overcoming therapeutic resistance mechanisms.

Another frontier explored by City of Hope’s research includes a first-in-human phase 1 study of ABBV-969, a novel therapeutic targeting metastatic castration-resistant prostate cancer (mCRPC). The investigation covers safety, pharmacokinetics, and preliminary efficacy metrics, aiming to carve a new pathway in prostate cancer management by exploiting molecular vulnerabilities unique to advanced disease phenotypes.

Intricately linking microbiome science with immuno-oncology, a standout study evaluates microbial dysbiosis as a biomarker predicting response to CBM588 when used alongside immune checkpoint blockade (ICB) therapies for metastatic renal cell carcinoma (mRCC). This innovative research adds a layer of complexity to personalizing cancer immunotherapies, suggesting that microbial ecosystem modulation could potentiate therapeutic efficacy and patient outcomes.

City of Hope’s commitment to combining molecularly targeted agents is further embodied in the randomized phase II SWOG S2001 trial, comparing the use of olaparib plus pembrolizumab with olaparib monotherapy as maintenance strategies in metastatic pancreatic cancer patients harboring germline BRCA1 or BRCA2 mutations. This trial hones in on synergistic immuno-genomic approaches to combat notoriously aggressive and refractory pancreatic tumors.

In parallel, dose-finding results emerging from a phase 1/2 study of tegavivint, a downstream Wnt/β-catenin pathway inhibitor, in advanced hepatocellular carcinoma (aHCC) highlight efforts to disrupt key oncogenic signaling nodes. Given the canonical Wnt pathway’s critical role in tumor proliferation and survival, these findings present promising avenues for targeting hepatobiliary malignancies often resistant to current interventions.

City of Hope does not merely contribute abstracts; it drives plenary discussions shaping contemporary oncology thought. For instance, the phase 3 LIBERTTO-432 trial evaluation of adjuvant selpercatinib in stage IB-IIIA RET fusion-positive non-small cell lung cancer (NSCLC) demonstrates improved event-free survival, emphasizing precision oncology’s expanding role even in early-stage disease.

Leading voices from City of Hope, such as Dr. Kristin Higgins, Chair and Moderator of a lung cancer case-based panel, dissect complex treatment pathways in ALK-positive NSCLC, navigating therapeutic decisions from early to advanced stages. Concurrently, hematologic malignancies expert Dr. Amrita Krishnan moderates critical discussion around treatment depth and risk in multiple myeloma, reflecting the center’s multifaceted expertise.

Immunotherapy continues to be a central theme with Dr. Tycel Phillips summarizing strategies to tailor immune interventions for relapsed lymphoma, reflecting the growing implications of bispecific antibodies, checkpoint inhibitors, and cellular therapies in refractory settings.

Prostate cancer management is also refined under City of Hope’s stewardship, as Dr. Tanya Dorff presents a comprehensive overview of personalized treatments spanning the entire disease spectrum, underscoring innovations that integrate genomic profiling, novel agents, and therapeutic sequencing.

The clinical exposition is complemented by educational sessions, such as those led by Dr. Charles Nguyen, who unpacks frontline therapeutic strategies in papillary renal cell carcinoma, a subtype demanding precise molecularly guided treatments.

City of Hope’s continued influence is mirrored by institutional honors, including Dr. John Carpten receiving the prestigious 2026 Allen Lichter Visionary Leader Award from ASCO. His groundbreaking work in cancer genomics and precision medicine has shaped strategic national research agendas and exemplifies the visionary leadership driving City of Hope’s mission.

The recognition extends to newly inducted Fellows of the American Society of Clinical Oncology (FASCO) from City of Hope, acknowledging sustained leadership and contributions in oncology care, research, and education. Drs. Arjun Gupta, Tanya Dorff, and Walter Stadler represent the breadth of expertise and dedication within this national oncology powerhouse.

City of Hope’s integrated approach, converging innovative research, clinical trials, and educational leadership, reinforces its position at the vanguard of oncology. Their expansive portfolio presented at ASCO 2026 not only charts the current science but shapes future paradigms designed to deliver therapies that are more personalized, tolerable, and efficacious.

The developments set forth by City of Hope’s research teams epitomize the crossroads of technological progress and medical ingenuity, heralding an era where cancer care transcends traditional boundaries and embodies tailored precision that elevates patient survival and quality of life.

As ASCO 2026 unfolds, City of Hope’s contributions are poised to inspire novel treatment algorithms, inform policy decisions, and galvanize the oncology community towards breakthroughs that reverberate across the spectrum of cancer biology and therapeutics.

Subject of Research: Cancer immunotherapy, precision medicine, novel therapeutic strategies, hematologic malignancies, solid tumors.

Article Title: City of Hope Scientists Unveil Pioneering Advances in Cancer Treatment at ASCO 2026.

News Publication Date: 2026.

Web References: https://www.cityofhope.org/asco-2026

Keywords: Immunotherapy, Precision Medicine, Metastatic Cancer, Hematologic Malignancies, Bispecific Antibodies, Cancer Genomics, Clinical Trials, Biomarkers, Wnt/β-catenin Inhibition, Immune Checkpoint Blockade, Prostate Cancer, Pancreatic Cancer.

A key focus of the research has been on the multifaceted roles of RNA chemical modifications in driving cancer behavior. More than 170 distinct RNA modifications have now been cataloged, including prominent types like N6-methyladenosine (m6A), 5-methylcytosine (m5C), and pseudouridine. These modifications regulate cellular processes by determining RNA localization, stability, and translational efficiency, thereby influencing protein synthesis. Systems biology investigators Dr. Xiaolan Deng and Dr. Jianjun Chen have provided a comprehensive framework linking specific RNA regulators to oncogenic pathways. Their work emphasizes the transformative potential of targeting RNA modifications as precise biomarkers and therapeutic targets, heralding a new era of RNA-centric precision oncology.

Concurrently, a pivotal clinical investigation led by radiation oncologist Dr. Kristin Higgins has reshaped the strategy for administering immunotherapy in limited-stage small cell lung cancer (SCLC). Despite high hopes, concurrent use of immune checkpoint inhibitors alongside chemoradiation failed to yield survival benefits or improved tumor control. Instead, delayed immunotherapy—administered subsequent to radiation—emerged as the more efficacious approach, suggesting that the immunomodulatory dynamics of timing govern therapeutic outcomes. These findings refine clinical protocols for integrating powerful immuno-oncology agents in aggressive lung malignancies.

In the realm of neurological disorders, City of Hope scientists achieved a striking preclinical milestone by demonstrating that human stem cell–derived brain cells can halt and reverse pre-existing brain damage in a mouse model of Canavan disease. This fatal infantile leukodystrophy results from a deficiency of the enzyme aspartoacylase, compromising myelin synthesis and neural function. The transplanted engineered stem cells not only replenished the missing enzyme but promoted remyelination, enhanced brain tissue health, and improved motor function months post-treatment. Crucially, the intervention remained effective despite administration after symptom onset, a vital consideration given the diagnostic challenges in such neurodegenerative conditions.

The innovative application of artificial intelligence (AI) has further augmented disease management, with a novel machine learning model identifying socioeconomic and neighborhood determinants as primary predictors for missed lung cancer screening follow-ups. Led by surgeon-scientist Dr. Loretta Erhunmwunsee and AI specialist Dr. Kun-Han Lu, this approach moves beyond traditional risk factors like smoking history to encompass social determinants of health, enabling early identification of patients at risk for screening non-compliance. This paradigm shift holds the potential to tailor community outreach and navigation efforts, ultimately improving early lung cancer detection.

Immunological research at City of Hope has unveiled a previously unrecognized subset of CD8+ T cells expressing CD318, exhibiting regulatory properties pivotal for tempering immune responses. Contrary to long-held dogma restricting immune regulation to certain cell types, this study led by immunologist Dr. Helena Reijonen reveals these CD318-positive cytotoxic T cells function like immune brakes, preventing excessive or aberrant immune activation. Understanding their role could lead to novel therapies for autoimmune diseases such as type 1 diabetes by enhancing immune tolerance mechanisms.

Further expanding the landscape of immune regulation, investigators discovered the protein TDRD3 as an essential orchestrator in the differentiation of induced regulatory T cells (iTregs). iTregs serve as critical suppressors of immune inflammation, and the absence of TDRD3 culminated in systemic inflammatory phenotypes in aging mouse models. This work, led by Dr. Yanzhong “Frankie” Yang and immunology professor Dr. Zuoming Sun, elucidates the epigenetic and molecular controls governing immune homeostasis. Targeting TDRD3 pathways offers translational promise for managing autoimmune and inflammatory disorders by reestablishing immune equilibrium.

Citizens of the oncology and biomedical fields have also recognized scientific leadership and excellence at City of Hope. Dr. John D. Carpten received the prestigious Allen Lichter Visionary Leader Award from the American Society of Clinical Oncology (ASCO), honoring his pivotal contributions in advancing cancer care. Likewise, Dr. Tanya B. Dorff plays a central leadership role in the 2026 ASCO Genitourinary Cancers Symposium, steering educational programming for prostate cancer innovations. These accolades underscore the commitment of City of Hope’s faculty to shaping the future of cancer research and clinical application.

Complementing individual achievements, ten City of Hope clinicians were named among the Los Angeles Business Journal’s “Leaders of Influence: 2026 LA Top Doctors.” Specialists spanning hematology, surgical oncology, urology, endocrinology, and pediatric oncology were recognized for their outstanding clinical expertise and dedication to patient care. This cohort includes Dr. Andrew Artz, Dr. Marwan Fakih, Dr. Thomas J. Gernon, Dr. Lorena Gonzalez, and other luminaries whose diverse disciplines underscore the center’s multidisciplinary strength.

Embedded within City of Hope’s mission is a commitment to translating benchside discoveries into tangible clinical benefits. Founded more than a century ago, City of Hope has pioneered breakthroughs that have revolutionized cancer therapeutics, diabetes management, and immunology. The institution’s integrated model spans a National Cancer Institute-designated comprehensive cancer center, expansive clinical networks, and robust academic and philanthropic infrastructures, ensuring continuous progress in life-saving science.

Collectively, these advancements reflect a vibrant ecosystem at City of Hope, where multidisciplinary collaboration, technological innovation, and patient-centered research converge. By elucidating molecular underpinnings of cancer, neurodegeneration, and immune regulation, scientists are forging pathways toward precision medicine that promises to transform outcomes for some of the most challenging diseases. The integration of AI-driven analytics, stem cell technologies, and immunologic insights illustrates a forward-looking agenda poised to accelerate discoveries from the laboratory to the bedside.

Subject of Research:
Article Title:
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Image Credits: City of Hope / Yanhong Shi Lab
Keywords: Cancer, Lung cancer, Stem cell research

Central to the challenge of treatment resistance in acute myeloid leukemia (AML) is the enigmatic role of the protein ALKBH1, as meticulously detailed by Dr. Jianjun Chen and his team. AML cells exploit a phenomenon known as codon-biased translation, enabling the preferential production of tumor-supportive proteins. ALKBH1 emerges as a key orchestrator in this process by remodeling the architecture of mitochondria, the cell’s energy hubs. This remodeling optimizes mitochondrial efficiency, supplying leukemia cells with an energetic advantage that bolsters survival and adaptation against targeted therapies like venetoclax. Experimental inhibition of ALKBH1, especially in concert with venetoclax treatment, yielded significant anti-leukemic effects with minimal toxicity in preclinical models, highlighting a promising therapeutic axis that could overcome refractory AML and perhaps other ALKBH1-driven malignancies.

Turning to breast cancer, researchers led by Dr. John Carpten have delivered an unprecedented genomic landscape analysis of triple-negative breast cancer (TNBC) in Black women. This aggressive subtype, characterized by the absence of estrogen, progesterone, and HER2 receptors, disproportionately affects younger African American women with poorer prognosis. By sequencing tumor genomes from over four hundred Black women, the study disclosed distinctive mutational patterns, notably a higher frequency of TP53 mutations and a lower prevalence of PIK3CA mutations compared to other populations. Notably, the tumors segregated into two distinct genomic subtypes with divergent clinical trajectories—one associated with younger age and better survival marked by a robust mutational burden, and another linked to older age, elevated body mass index, attenuated immune responses, and poorer outcomes. These findings not only provide crucial insights into the molecular underpinnings of racial disparities in TNBC but also point towards tailored immunotherapeutic and targeted intervention strategies that could enhance survival in this underserved demographic.

Immunotherapy innovation took a leap forward with research into Th9 cells, a subset of helper T cells endowed with formidable anti-tumor activity. The City of Hope team, including Drs. Michael Caligiuri and Shoubao Ma, dissected the molecular brakes imposed by YTHDF2, an RNA-binding protein that regulates the development and function of Th9 cells. By genetically removing YTHDF2, they unleashed a proliferation of hyperactive Th9 cells exhibiting enhanced tumor-killing capabilities. This revelation opens new avenues for CAR T cell engineering, where reprogrammed Th9 cells can be harnessed to confront solid tumors—long considered impregnable by traditional CAR T therapies. Such enhancements could dramatically expand the reach and potency of cellular immunotherapeutics.

In a striking and unconventional pivot, City of Hope scientists have developed a CAR T cell therapy for glioblastoma that incorporates chlorotoxin, a peptide derived from scorpion venom, to target malignant brain tumors with precision. This innovative approach, pioneered by neurosurgeon Dr. Behnam Badie and colleagues, exploits chlorotoxin’s natural affinity for glioblastoma cell membranes without harming normal brain tissue. Early-phase clinical trials demonstrated safety and tolerability, with CAR T cells persisting in the tumor microenvironment and achieving temporary disease stabilization in most patients despite the aggressive nature of glioblastoma. This pioneering work embodies a fusion of natural toxin biology and synthetic immunotherapy, offering renewed hope against one of the deadliest cancers known.

Further advancing the fight against recalcitrant tumors, City of Hope researchers engineered an oncolytic virus named CF33-hNIS-antiPDL1 designed to infiltrate and dismantle the immunosuppressive microenvironment of pancreatic ductal adenocarcinoma (PDAC). This virus not only selectively infects and lyses pancreatic cancer cells but also expresses a checkpoint inhibitor targeting PD-L1, a protein that tumors exploit to evade immune detection. In preclinical models, this dual-action viral therapy significantly curtailed tumor growth, enhanced immune cell infiltration, and prolonged survival. Notably, intraperitoneal administration of CF33-hNIS-antiPDL1 yielded superior efficacy over systemic delivery, highlighting the importance of delivery routes in virotherapy. These findings propel CF33 derivatives as potent candidates in the quest to breach pancreatic cancer’s formidable immune defenses.

Together, these advances epitomize the sophisticated convergence of molecular biology, genomic medicine, immunoengineering, and virotherapy in contemporary oncology research. City of Hope’s integrated model—from deep mechanistic studies, through translational preclinical evaluation, to pioneering clinical trials—embodies a paradigm shift towards personalized, multi-dimensional cancer care. The elucidation of ALKBH1’s mitochondrial modulation in AML enriches the therapeutic arsenal against drug resistance, while the human genomic insights into TNBC highlight the critical need to address racial disparities with precision medicine. CAR T cell evolutionary leaps through Th9 enhancement and venom-based targeting redefine immunotherapy’s potential against formidable solid tumors. Lastly, the marriage of viral engineering and checkpoint blockade holds promise to transform the grim landscape of pancreatic cancer prognosis.

These breakthroughs, supported by national and international collaborations, including licensing partnerships with biotechnology firms, reaffirm City of Hope’s status as a beacon of innovation in cancer research. Ensuring equitable access to these therapies and continued inclusion of diverse populations in clinical studies remain imperative. As these novel strategies progress from bench to bedside, they embody a collective promise to redefine cancer survivorship and ultimately translate scientific insight into lasting hope for patients worldwide.

Subject of Research: Acute Myeloid Leukemia, Triple-negative Breast Cancer, CAR T Cell Therapy, Glioblastoma, Pancreatic Cancer

Article Title: City of Hope Unveils Molecular and Therapeutic Innovations to Combat Resistant Cancers

News Publication Date: Not specified

Web References:
– https://www.cityofhope.org/
– https://aacrjournals.org/cancerdiscovery/article/10.1158/2159-8290.CD-24-1043/763931/ALKBH1-drives-tumorigenesis-and-drug-resistance
– https://www.nature.com/articles/s41588-025-02322-y
– https://www.nature.com/articles/s41590-025-02235-2
– https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00375-1
– https://www.sciencedirect.com/science/article/pii/S075333222500602X

References:
– Chen, J. et al. ALKBH1 Drives Tumorigenesis and Drug Resistance in AML. Cancer Discovery.
– Carpten, J. et al. Genomic Landscape and Distinct Subtypes of Triple-Negative Breast Cancer in Black Women. Nature Genetics.
– Caligiuri, M., Ma, S. YTHDF2 Regulates Th9 Cell Development and Enhances CAR T Immunotherapy. Nature Immunology.
– Badie, B., Barish, M., Brown, C. CLTX-CAR T Cells for Glioblastoma: Early Clinical Trial Outcomes. Cell Reports Medicine.
– Woo, Y. et al. CF33 Oncolytic Virus Engineered to Block PD-L1 in Pancreatic Cancer. Biomedicine & Pharmacotherapy.

Image Credits: City of Hope

Keywords: Myeloid leukemia, Triple-negative breast cancer, CAR T therapy, Glioblastoma, Pancreatic cancer, ALKBH1, TP53 mutation, YTHDF2, Chlorotoxin, Oncolytic virus, Immune checkpoint blockade, Cancer drug resistance

LOS ANGELES — City of Hope®, one of the largest and most advanced cancer research and treatment organizations in the U.S., launched an innovative national clinical trials model to expand access to emerging life-saving cancer treatments to more patients across the country. This model simplifies the opening of new trial locations and streamlines patient enrollment with the goal of accelerating the development of new cancer treatments and improving clinical care.  

As the first academic center with a national clinical trial network and a large and diverse patient population served through a national network of advanced cancer centers, City of Hope will offer unprecedented access to lifesaving care, novel therapies, and clinical decision-making expertise. Through the model, City of Hope operates a single centralized hub which has multiple research locations, enabling the organization to open a clinical trial across multiple states simultaneously with this centralized support. The operational efficiency of this national model reduces patient enrollment times, increases enrollment numbers and ensures patients across a wide geographic footprint have access to an extensive portfolio of leading-edge treatment options.  

“Our North Star is to offer all our patients, regardless of where they live, the opportunity to participate in clinical trials, which provide them with promising new treatment options long before they become the standard of care,” said Edward S. Kim, M.D., M.B.A., FACP, FASCO, vice physician-in-chief, City of Hope National Medical Center and system director, Clinical Trials.  “Whether a trial is sponsored by the NIH, by a pharmaceutical company or is studying an investigational medicine developed right here at City of Hope, the remarkable function of our new national model is the ability for a single institution to enroll patients in communities who don’t typically have access to these types of leading-edge trials. By building a single yet scalable model, we can now deliver on our vision to create access and care closer to those living with cancer.” 

Typically, clinical trial models face significant limitations, including where and when a clinical trial can open, the timely enrollment of patients, available resources and on-site expertise to support the trial. City of Hope’s new model was built to support a distributed, digitally connected network of clinical trial sites. The unique structure of the model means it can accommodate rapid expansion across the U.S. without needing to overhaul core systems. 

Another key differentiator of the model – it allows investigators to bring groundbreaking science to every City of Hope location, boosting the organization’s mission to make hope a reality for anyone touched by cancer or diabetes. 

Building on a Legacy
For over 100 years, City of Hope has served Los Angeles communities. Today, with 37 locations across the U.S., including premier cancer centers in Orange County, Phoenix, Chicago and Atlanta, millions of Americans of diverse backgrounds are now within 90 minutes of a City of Hope site. As a legacy organization known for its powerhouse research and clinical care — the expanded footprint called for a novel approach to its clinical trial framework. 

“Currently, the gap between those who can access therapeutic breakthroughs and those who can’t is widening and in many cases the issue is simply due to the zip code they reside in. Through innovation, City of Hope is removing barriers and bridging geographic divides, bringing our renowned clinical excellence closer to all patients,” said Marcel van den Brink, M.D., Ph.D., president, City of Hope Los Angeles and City of Hope National Medical Center and the Deana and Steve Campbell Chief Physician Executive Distinguished Chair. “This unique approach to clinical research, along with supportive care programs and personalized medicine, ensures every City of Hope patient can access the latest cancer advances.”

Early Success
In the first few months since launch, nine clinical trials across solid tumors and blood cancers are running at 12 City of Hope sites. With centralized support, patient enrollment is ahead of expectations and the studies are expected to reach their targets. 

“We are thrilled to collaborate with City of Hope to help pioneer this leading-edge model,” said John Pagel, M.D., Ph.D., Senior Vice President, Clinical Development, Global Head of Hematology, Eli Lilly and Company. “The new centralized model saves time and resources and has potential to lead to higher quality research and contribute to our ability to rapidly advance scientific innovation that can make a meaningful difference for patients.” 
 
A Phase 2 clinical trial of Lilly’s therapy for relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma is now open at eight City of Hope locations across the country.

Developing New Tools for Tomorrow’s Needs 
To deliver a scalable and unified system, regulatory, operational and digital frameworks were developed to accommodate new trial sites anywhere in the world. City of Hope experts are also developing AI and predictive tools to incorporate into the portal to help determine where certain patients reside and identify the best locations for each trial.

“City of Hope has built an all-in-one model that can not only keep up with the pace of our scientific research and clinical innovations, but also support our investigators and collaborators, and ultimately how we deliver care and most importantly, hope, to our patients, regardless of where they are,” Dr. Kim said.

To learn more about the clinical trials model contact: trialintake@coh.org. For details on participating in a clinical trial call: 855-970-2654.

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About City of Hope
City of Hope’s mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked among the nation’s top cancer centers by U.S. News & World Report at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training and innovation initiatives. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHope^TM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn.
 

One of the most compelling new clinical trials launched by City of Hope involves a nonsurgical treatment strategy for rectal cancer. This Phase 2 study investigates the efficacy of combining the FOLFOX chemotherapy regimen—consisting of fluorouracil, oxaliplatin, and leucovorin calcium—with immunotherapeutic agents botensilimab and balstilimab. Significantly, this combination is administered to patients with localized rectal adenocarcinoma who have not undergone surgery, aiming to evaluate whether this regimen can achieve tumor eradication without the need for conventional radiation or invasive surgery, which often result in long-term urinary and bowel dysfunction. This trial embodies a paradigm shift toward organ preservation and improved quality of life for patients confronting rectal cancer.

In parallel, City of Hope has initiated a Phase 1 trial exploring the use of triapine, an oral ribonucleotide reductase inhibitor, in conjunction with radiation therapy for patients with recurrent glioblastoma and astrocytoma. These malignancies represent some of the most intractable brain tumors, notorious for treatment resistance and poor prognosis. By inhibiting the enzyme critical for DNA synthesis, triapine disrupts tumor cell replication and potentially enhances radiosensitivity. The primary objective is dose-escalation to establish safety and tolerability, but investigators are also monitoring tumor response and symptom alleviation. Success in this trial could open new therapeutic avenues for a cancer type with limited options.

Advancing the frontier of diagnostic oncology, City of Hope researchers have developed a promising liquid biopsy for early gastric cancer detection. The innovation leverages exosome-derived microRNAs (miRNAs) as sensitive biomarkers retrievable from blood samples. Collaborating with institutions in high-incidence regions such as Japan and South Korea, the team applied machine learning algorithms to identify a signature panel of 10 miRNAs capable of detecting early-stage gastric cancer with 95% accuracy. This noninvasive approach, branded as DESTINEX, could revolutionize screening protocols, circumventing the limitations of current endoscopy-based methods by offering a less invasive, more accessible, and cost-effective option—particularly pertinent for populations where widespread endoscopic screening is impractical.

Immunological restoration post-cancer treatment is another critical domain illuminated by City of Hope’s research. Investigators have spotlighted a subset of hematopoietic stem cells characterized by low expression of the Kit receptor (Kit^lo HSC), which plays a pivotal role in rejuvenating thymic function and thereby enhancing T cell reconstitution after allogeneic hematopoietic cell transplantation—a common therapeutic procedure for hematological malignancies. Experimental murine models revealed that Kit^lo HSCs promote thymic recovery and boost adaptive immunity, even counteracting age-associated thymic decline, through complex genomic regulatory networks involving key transcription factors such as ZBTB1. These findings suggest that targeting or augmenting Kit^lo HSC populations could be transformative in improving immune resilience following cytotoxic therapies.

The intersection of social determinants and cancer epidemiology also emerges as a critical area of inquiry. A large-scale epidemiological analysis by City of Hope highlights how residential segregation correlates with an increased lung cancer incidence among Black Americans. Using data from over 71,000 individuals, the study identified that living in racially less segregated neighborhoods corresponded with a lower lung cancer risk. Factors such as menthol cigarette usage—a product disproportionately marketed to Black communities—and environmental air pollution were implicated as mediators. This research not only underscores the significance of structural racism in health disparities but also informs targeted public health interventions and policy reforms aimed at mitigating these inequities.

Beyond clinical and societal investigations, City of Hope is celebrating landmark recognition in diabetes research with faculty members receiving prestigious awards for their contributions to understanding metabolic diseases. These honors reflect the institution’s broad commitment to exploring the molecular underpinnings of diabetes and its intersections with cancer biology, thereby fostering interdisciplinary innovation.

The institution’s research ecosystem continues to thrive under substantial funding awards from federal agencies. Noteworthy grants include a $6.2 million NIH/NCI award supporting advances in natural killer cell biology, a $4.1 million project probing cellular stress pathways affecting pancreatic beta cells, and multimillion-dollar funds allocated to study immune cell development and epigenetic regulation within metabolic contexts. These investments underpin ongoing efforts to elucidate fundamental cellular mechanisms with translational potential.

Taken together, City of Hope’s multifaceted research portfolio demonstrates the power of integrating clinical trial innovation, biomarker discovery, immunology, epidemiology, and basic science. The institution’s work not only seeks to improve individual patient outcomes but also addresses broader public health challenges, aiming to make hope a tangible reality across diverse populations afflicted by cancer, diabetes, and other chronic diseases.

Subject of Research: Cancer treatment innovation, liquid biopsy diagnostics, immune system recovery, social determinants of lung cancer risk, diabetes and metabolism research.

Article Title: City of Hope Advances Cancer Care with Novel Clinical Trials, Diagnostic Innovations, and Insights into Immune Recovery and Health Disparities

News Publication Date: Not specified

Web References:

• Rectal Cancer Trial: https://clinicaltrials.gov/study/NCT06780787
• Glioblastoma Trial: https://clinicaltrials.gov/study/NCT06860594
• Gastric Cancer Biomarker Study: https://jamanetwork.com/journals/jamasurgery/fullarticle/2837074
• Immune Recovery Research: https://www.nature.com/articles/s41467-025-61125-1
• Lung Cancer and Segregation Study: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2835843

References:

• Selection of peer-reviewed journal articles linked above.

Image Credits: City of Hope

Among the most compelling studies featured is a large-scale retrospective analysis evaluating the safety of rechallenging metastatic breast cancer patients with trastuzumab-deruxtecan (T-DXd) following episodes of low-grade interstitial lung disease (ILD). T-DXd, an antibody-drug conjugate approved for HER2-positive and HER2-low breast cancers, entails a rare but significant risk of ILD. This study of 712 patients provides robust real-world evidence that carefully managed rechallenge post-ILD resolution is feasible and can confer substantial clinical benefit. Importantly, steroid administration accelerated radiographic ILD improvement, underscoring timely immunomodulatory interventions to mitigate pulmonary toxicity.

City of Hope researchers meticulously gathered detailed data including patient demographics, T-DXd dosing schedules, steroid use, imaging results, and outcomes from rechallenge protocols. Approximately 9% of treated patients developed ILD, with 47 individuals undergoing drug rechallenge primarily after grade 1 (asymptomatic) ILD. Notably, the recurrence of ILD was predominantly low-grade, with no fatal-grade 5 events recorded. Following rechallenge, patients maintained therapy for a median duration exceeding seven months, suggesting durable benefit despite initial pulmonary complications. These findings provide a critical evidence base to inform clinical decision-making in managing T-DXd-associated ILD.

Shifting focus to genitourinary oncology, City of Hope investigators revealed novel insights into the genomic evolution of renal cell carcinoma (RCC) and its recurrence patterns. Despite curative-intent nephrectomy, about one-fifth of RCC patients experience relapse, posing a clinical challenge. Through precision medicine approaches, the team analyzed pretreatment tumor tissue from 754 patients enrolled in the IMmotion010 Phase 3 trial, which assessed the adjuvant efficacy of the monoclonal antibody atezolizumab. While the trial overall did not demonstrate prevention of disease recurrence, genomic profiling delineated molecular subgroups, particularly those with high KIM-1 biomarker expression and enriched tumor effector (Teff) immune cells, who exhibited prolonged disease-free survival with atezolizumab.

This integrative genomic and transcriptomic profiling illuminates the heterogeneity underlying RCC recurrence and response to immunotherapy. Cluster 6 tumors, characterized by stromal and proliferative signatures, represented a distinct subset deriving benefit from adjuvant checkpoint inhibition. Furthermore, longitudinal analysis through whole-transcriptome sequencing at baseline and recurrence revealed dynamic genomic shifts, offering mechanistic explanations for disease progression. These discoveries pave the way for refined biomarker-driven patient selection, enabling personalized immunotherapeutic strategies that may effectively delay or prevent relapse.

In colorectal cancer, a notoriously immunoresistant malignancy due to prevalent microsatellite stability (MSS), City of Hope’s Phase 2 trial of dual checkpoint inhibition showcases encouraging preliminary results. The combination of Vilastobart (XTX101), an investigational immune checkpoint modulator, with atezolizumab demonstrated tumor shrinkage in patients with advanced MSS colorectal cancer—a group traditionally unresponsive to immunotherapy. Approximately 27% of patients without hepatic metastases achieved partial responses, accompanied by notable reductions in circulating tumor DNA levels, bolstering evidence of anti-tumor activity.

This clinical evaluation, involving heavily pretreated patients, advances the frontier of immuno-oncology by overcoming established resistance mechanisms. The favorable safety profile, marked by low occurrences of severe immune complications and minimal treatment discontinuations, further substantiates the regimen’s potential. Vilastobart’s development by Xilio Therapeutics, co-founded by City of Hope scientist Dr. John Williams, exemplifies translational innovation bridging scientific discovery to clinical application. These data may herald a new era of combinatorial immunotherapies tailored for colorectal cancer subsets.

Turning attention to prostate cancer, a comprehensive observational study led by Dr. Alan H. Bryce leveraged extensive real-world data comprising over 68 million U.S. Medicare and Medicaid beneficiaries. This investigation scrutinized cardiovascular outcomes among metastatic castration-resistant prostate cancer (mCRPC) patients treated with either abiraterone acetate or enzalutamide, two primary androgen-targeting agents. Findings reaffirmed clinical trial signals that abiraterone acetate is associated with a significantly elevated risk of cardiovascular events—including myocardial infarction, stroke, and arrhythmias—compared to enzalutamide, especially in patients without prior chemotherapy.

Strikingly, the risk of all-cause mortality was also heightened in the abiraterone cohort regardless of cardiovascular disease history. These real-world insights emphasize the need for vigilant cardiovascular risk stratification and therapeutic selection in this vulnerable population. By integrating large-scale epidemiological data, the study transcends the limitations of controlled clinical trial environments, offering pragmatic guidance for optimizing treatment algorithms that balance oncologic efficacy with cardiovascular safety.

Collectively, City of Hope’s multifaceted research portfolio presented at ASCO 2025 underscores the institution’s leadership in pioneering personalized oncology solutions rooted in rigorous science and clinical pragmatism. Their work exemplifies how combining molecular diagnostics, real-world evidence, and innovative trial designs accelerates the translation of cutting-edge therapies to patient benefit. As the oncology community converges in Chicago and online, these findings promise to reshape therapeutic landscapes, inspire new collaborations, and invigorate efforts to enhance survival and quality of life for cancer patients worldwide.

City of Hope’s ongoing commitment encompasses not only breakthrough treatment modalities but also the integration of supportive care interventions aimed at reducing cancer risk and improving survivorship outcomes. By embracing a holistic research agenda that spans breast, kidney, colorectal, and prostate cancers, the institution advances the broader mission of transforming hope into reality through science-driven innovation. The upcoming ASCO presentations will undoubtedly catalyze further advancements and highlight the critical role of multidisciplinary expertise in confronting cancer’s complexities.

As oncology continues to evolve at a rapid pace, real-world data, sophisticated genomics, and novel biologic agents are at the forefront of redefining standards of care. City of Hope’s research initiatives exemplify how harnessing these tools can generate actionable insights, leading to safer, more effective, and increasingly individualized treatment protocols. The 2025 ASCO Annual Meeting will serve as a dynamic platform to disseminate these achievements, engage global experts, and foster the collective progress necessary to conquer cancer’s challenges in the decades ahead.

Subject of Research: Novel cancer treatment approaches, targeted therapies, and supportive care interventions focusing on breast, genitourinary, and gastrointestinal cancers.

Article Title: City of Hope Unveils Groundbreaking Cancer Therapies and Precision Medicine Insights Ahead of 2025 ASCO Annual Meeting

News Publication Date: Not explicitly stated; derived from event date (May 30–June 3, 2025)

Web References:

• ASCO Annual Meeting: https://meetings.asco.org/2025-asco-annual-meeting/
• Clinical trials: NCT03024996 (IMmotion010), NCT04896697

References: Information derived from City of Hope press release and abstracts listed for the 2025 ASCO Annual Meeting.

Image Credits: City of Hope

Keywords: Breast cancer, renal cell carcinoma, colorectal cancer, prostate cancer, trastuzumab-deruxtecan, atezolizumab, Vilastobart, immune checkpoint inhibitors, real-world data, cancer genomics, cardiovascular safety, metastatic cancer

The theme for this year’s ASCO assembly, “Driving Knowledge to Action. Building a Better Future,” underscores the critical nexus between cutting-edge research and patient-centered clinical application. City of Hope’s delegation is poised to contribute robust data sets and innovative research paradigms that spotlight precision oncology, novel therapeutic agents, and advanced management approaches for various malignancies including breast, pancreatic, colorectal, prostate, kidney, and hematologic cancers. Moreover, the emphasis on integrative and supportive care, such as palliative interventions, marks a progressive step towards holistic cancer treatment pathways that prioritize quality of life alongside survival metrics.

Central to City of Hope’s presentations are several key oral abstract and clinical symposium sessions that dissect tumor biology and therapeutic resistance in high-risk renal cell carcinoma. The IMmotion010 study, a randomized phase 3 trial exploring adjuvant atezolizumab versus placebo, will unveil comprehensive genomic characterizations of baseline and post-progression tumors. This analysis promises to elucidate mechanisms of immune evasion and tumor evolution, potentially guiding biomarker-driven treatment algorithms in kidney cancer. Leading this discourse is Dr. Sumanta Kumar Pal, a seasoned medical oncologist with extensive expertise in therapeutic research at City of Hope.

Complementing the genomic insights, City of Hope also emphasizes symptom science and palliative care, acknowledging the indispensable role these disciplines play in oncology. Dr. Tanyanika Phillips will chair a session focusing on the management of cancer-related symptoms and the integration of palliative care principles within standard oncology practice. This aligns with the growing recognition that addressing treatment side effects and symptom burden is fundamental to enhancing patient outcomes and curbing healthcare costs.

Dr. Heather Hampel’s involvement as chair and panelist in a session dedicated to hereditary cancer demonstrates City of Hope’s commitment to genetic risk stratification and precision prevention. By delving deeper into hereditary cancer risk and its clinical repercussions, the session will underscore advances in genetic counseling and germline testing that can personalize cancer surveillance and prophylactic strategies.

Rapid oral abstract sessions will highlight groundbreaking work in breast cancer therapy and hematologic malignancies. The investigation led by Dr. Hope S. Rugo into treatment rechallenge following trastuzumab-deruxtecan-related interstitial lung disease addresses a critical safety and efficacy question in metastatic breast cancer management. Understanding how to safely reintroduce this potent antibody-drug conjugate after pulmonary toxicity could expand therapeutic options for patients with resistant disease.

In leukemia research, Dr. Ibrahim T. Aldoss presents a post hoc analysis from the Phase 3 PhALLCON trial regarding minimal residual disease (MRD) negativity after induction therapy. MRD status serves as a highly sensitive biomarker predictive of relapse and survival, and optimizing treatment to achieve MRD negativity is a paramount goal in acute leukemia management. These findings can expedite the adoption of MRD-guided therapeutic decision-making.

Innovations in myeloma treatment will be critically discussed through City of Hope’s participation as a discussant in sessions exploring novel therapeutic avenues targeting plasma cell dyscrasias. Dr. Amrita Krishnan’s expertise enhances the dialogue surrounding emerging regimens and biomarker-driven interventions aimed at improving long-term disease control and patient quality of life in multiple myeloma.

Educational sessions curated by City of Hope further underscore emerging challenges in oncology. Dr. Hope S. Rugo’s presentation on managing endocrine toxicities serves to equip oncologists with best practices for mitigating adverse effects related to novel breast cancer therapies. This is pivotal as new agents with complex side effect profiles enter clinical use, requiring nuanced management strategies to maintain treatment adherence.

Pediatric oncology survivors’ morbidity reduction is addressed in a session led by Dr. Saro H. Armenian, who advocates for personalized intervention approaches. This focus highlights survivorship care as a critical extension of cancer therapy, addressing long-term consequences of childhood cancer treatment through tailored risk assessment and supportive care techniques.

Integrative oncology is also represented, with Dr. Krisstina Gowin presenting evidence-based guidelines for the management of cancer-associated pain, fatigue, and depression. By operationalizing ASCO’s supportive care guidelines into real-world practice, these sessions promote holistic, patient-centered care models that integrate conventional and complementary modalities.

Poster presentations extend the scope of City of Hope’s research portfolio, showcasing innovative clinical trial data across metastatic breast cancer, pancreatic ductal adenocarcinoma, colorectal cancer, and genitourinary malignancies. Notably, the NAPOLI 3 Phase 3 trial final overall survival analysis in metastatic pancreatic cancer, presented by Dr. Vincent Chung, offers fresh perspectives on treatment efficacy and long-term survival characteristics. Similarly, evaluations of novel immunotherapies and combinatorial regimens in kidney and prostate cancers provide important insights into optimizing sequencing and combination strategies.

Recognition of City of Hope faculty members such as Drs. Lorna Rodriguez-Rodriguez and Stacy W. Gray, who were inducted as fellows of the American Society of Clinical Oncology (FASCO), reflects the institution’s dedication to leadership in oncology research, education, and clinical excellence. This honor acknowledges their pivotal roles in fostering innovation and advancing standards of care to conquer cancer effectively.

City of Hope’s integrated research-to-practice model, underscored by its NCI-designated comprehensive cancer center, continues to influence oncology globally. The institution’s contributions at the 2025 ASCO Annual Meeting epitomize a mission-driven commitment to transforming complex cancer data into actionable clinical applications that improve patient survival and wellbeing. By converging basic science, translational research, and clinical expertise, City of Hope underscores the future of oncology—a future where knowledge unequivocally drives transformative cancer care.

As oncology confronts the challenges of heterogeneity, resistance mechanisms, and survivorship complexities, City of Hope’s broad research landscape—from molecular tumor characterization to supportive care innovation—foreshadows a new horizon in personalized and effective cancer management worldwide.

Subject of Research: Oncology research and clinical advancements across multiple cancer types, including renal cell carcinoma, breast cancer, pancreatic cancer, colorectal cancer, prostate cancer, kidney cancer, blood cancers, and supportive care modalities.

Article Title: City of Hope Unveils Pioneering Oncology Research at 2025 ASCO Annual Meeting

News Publication Date: Not specified in the provided content

Web References:

• https://meetings.asco.org/2025-asco-annual-meeting
• https://www.cityofhope.org/

References: Not explicitly provided in the content

Image Credits: Not provided

Keywords: Oncology, Cancer Research, Precision Medicine, Immunotherapy, Hematologic Malignancies, Breast Cancer, Pancreatic Cancer, Colorectal Cancer, Prostate Cancer, Kidney Cancer, Clinical Trials, Supportive Care, Palliative Care

Central to the presentations was an FDA-approved breakthrough immunotherapy drug known as penpulimab, designed to combat recurrent or metastatic nasopharyngeal carcinoma, a rare yet regionally prevalent cancer of the upper throat. The phase 3 multinational randomized clinical trial demonstrated that treatment with penpulimab, in conjunction with standard chemotherapy, significantly prolonged disease control times compared to chemotherapy alone, revealing a 55% reduction in the risk of disease progression. This anti-PD-1 antibody boasts a modified molecular architecture aimed at enhancing therapeutic efficacy while mitigating immune-related adverse effects, a strategy that could resonate across diverse patient populations and cancer types.

The conference also saw City of Hope scientists employing avant-garde spatial transcriptomic techniques to illuminate the underpinnings of immune responses within complex tumor microenvironments. In aggressive high-grade serous ovarian cancer, researchers harnessed spatial mapping technologies to decipher variations in immune cell distribution and gene expression across tumors exhibiting differential responses to immune checkpoint inhibitors. This approach promises to refine patient stratification, enabling clinicians to predict and potentially improve immunotherapy responsiveness in a cancer subtype notorious for treatment resistance.

Expanding the study of tumor heterogeneity, investigations into metastatic hormone-sensitive prostate cancer highlighted the intertwining effects of ethnicity and biology. Leveraging digital spatial profiling, the research team identified differential expression of key protein targets such as Foxp3, PARP, and STING between Hispanic and non-Hispanic patient groups. These disparities could elucidate underlying variations in treatment efficacy, advocating for more inclusive clinical evaluations. Ongoing analyses aim to correlate protein expression profiles with therapeutic outcomes, paving the way for culturally and biologically informed oncology care.

In breast cancer research, an innovative AI-driven model was unveiled that integrates multimodal patient data far beyond conventional biomarkers to forecast recurrence-free survival accurately. The utilization of survival-based variational autoencoders, a sophisticated machine learning technique, enables the assimilation of genetic, clinical, and demographic data to yield robust prognostic insights. This AI framework not only anticipates disease outcomes with greater precision but also holds potential for guiding personalized therapy regimens, mitigating overtreatment, and sparing patients unnecessary toxicities.

A foray into the genetic landscape of early-onset colorectal cancer among Hispanic and Latino populations revealed unique molecular signatures using 10x Genomics Visium spatial transcriptomics. By precisely localizing gene activity within tumor architecture, this research shed light on the interaction between cancer cells and the immune milieu, offering explanations for aggressive disease behaviors that disproportionately affect these communities. The findings highlight the critical need for population-specific cancer research to bridge health disparities and inspire novel therapeutic avenues.

Associated with this, City of Hope researchers introduced the Precision Medicine Artificial Intelligence Agent (PM-AI), a conversational AI system capable of integrating clinical data, genomic information, and social determinants of health within an intuitive interface. PM-AI automates complex data analyses, making the synthesis of heterogeneous datasets accessible to researchers and clinicians alike. This represents a significant stride towards equitable precision oncology, as it factors in socio-economic variables that traditionally elude conventional clinical models but significantly influence patient outcomes.

Addressing the stubborn problem of therapeutic resistance in estrogen receptor-positive (ER+) breast cancer, a novel combination treatment emerged from integrative biological and computational investigations. Researchers found that resistant tumors rewire their apoptosis and proliferative signaling pathways, enabling survival despite cell cycle inhibitor therapies. The proposed combination of ribociclib, a CDK4/6 inhibitor, with afatinib, a growth factor receptor blocker, demonstrated durable suppression of cancer cell proliferation over time, opening promising therapeutic windows for overcoming resistance mechanisms.

Throughout the AACR meeting, City of Hope’s multidisciplinary teams displayed an impressive commitment to leveraging precision biology and translational research to tackle diverse cancer types under a unified framework consistent with the principles of personalized, equitable treatment. From ovarian to colorectal, prostate to breast cancer, their works exemplify how technological innovation and clinical insight converge to unravel cancer’s complexity and deliver hope where conventional therapies fall short.

Looking ahead, these pioneering studies not only propose actionable biomarkers and therapeutic strategies but also emphasize the crucial importance of integrating diverse genetic ancestries and social contexts into oncology research—a direction poised to enhance global cancer care standards. City of Hope’s fusion of spatial technologies, AI, and advanced clinical trials design signals an inflection point in how cancer is understood and managed, promising more effective, inclusive, and enduring treatment paradigms in the years to come.

To conclude, the concerted effort at City of Hope has yielded a compendium of cancer research breakthroughs, including FDA-approved immunotherapies, spatial mapping of tumor-immune interfaces, AI tools for integrative data analysis, and combination therapies targeting drug resistance. These findings collectively herald an era in which cancer treatment is as precise as it is compassionate, tailored to the genetic and societal nuances that define each patient’s battle with disease.

Subject of Research: Innovative cancer research encompassing immunotherapy, tumor microenvironment analysis, genetic profiling, AI applications in precision medicine, and overcoming drug resistance in major cancer types.

Article Title: City of Hope Unveils Transformative Advances in Cancer Biology and Precision Medicine at AACR Annual Meeting 2025

News Publication Date: April 2025 (Corresponding with AACR Annual Meeting 2025)

Web References:

• City of Hope: https://www.cityofhope.org
• AACR Annual Meeting Abstracts: https://www.abstractsonline.com/pp8/#!/20273/

Keywords: Cancer research, immunotherapy, nasopharyngeal carcinoma, spatial transcriptomics, AI in oncology, precision medicine, breast cancer, ovarian cancer, prostate cancer, colorectal cancer, tumor microenvironment, drug resistance

One of the overarching themes of City of Hope’s presentations is the integration of artificial intelligence (AI) and multiomics to decode the complex biology of tumors. Professor David W. Craig, an authority in integrative translational sciences, chairs the final plenary session titled “Opportunities in Predictive Oncology.” This session will explore emerging computational and biological strategies that leverage multi-level tumor data to refine precision oncology. Dr. Craig’s work particularly focuses on melding diverse data types—including genomic, proteomic, and spatial information—to dissect tumor heterogeneity and treatment resistance, fundamental barriers in effective cancer therapy.

Dr. Craig also helms an educational session dedicated to AI and data science, spotlighting how multi-scale, multi-modal integration enhances understanding of cancer’s genetic diversity. Highlighting methods such as spatial transcriptomics and single-cell genomics, this session illustrates how dissecting the spatial architecture within tumors reveals subclonal variations influencing tumor progression and therapeutic response. Graduate researcher Nina Song from Dr. Craig’s laboratory will present novel findings demonstrating the power of AI to fuse digital pathology with genomic data, offering unprecedented insights into aggressive cancers like glioblastoma, triple-negative breast cancer, and colorectal cancer.

Natural killer (NK) cells represent another focal point of City of Hope’s scientific agenda at AACR 2025. Michael A. Caligiuri, M.D., former president of City of Hope National Medical Center, chairs critical educational sessions on the biology and clinical translation of NK cells. These innate immune lymphocytes have emerged as potent anti-cancer effectors, capable of recognizing and eradicating transformed cells without prior sensitization. Dr. Caligiuri’s presentations will delve into molecular mechanisms regulating NK cell function and therapeutic strategies leveraging NK cells as immunotherapy agents, reflecting City of Hope’s leadership in harnessing innate immunity to combat cancer.

In addition to immunology, City of Hope scientists are pioneering research in precision medicine for underserved populations, an imperative often overlooked in cancer research. Postdoctoral scientist Francisco Carranza will unveil multi-omics analyses dissecting the MYC oncogene and WNT signaling pathway alterations in early-onset colorectal cancer among Hispanic/Latino patients. By integrating genomic and spatial transcriptomics technologies, this research elucidates the molecular underpinnings of cancer disparities and guides development of tailored diagnostics and treatments informed by ethnic diversity.

Precision artificial intelligence tools for clinical oncogenomics represent a further area of innovation. Assistant Professor Enrique Velazquez Villarreal and collaborators have developed PM-AI Agent, a conversational AI system designed to integrate extensive clinical, genomic, and social determinants of health data. This tool aims to facilitate equitable precision oncology by accounting for population-specific variables and social factors, providing clinicians with actionable insights that transcend traditional data silos. Such integrative approaches promise to reduce disparities and optimize therapeutic decision-making in complex cancer cases.

City of Hope’s clinical trial portfolio also features prominently at AACR 2025, highlighting advances in antibody-drug conjugates (ADCs) and immune checkpoint inhibitors. Hope Rugo, M.D., newly appointed director of the Women’s Cancers Program, will present on managing toxicities associated with emerging ADCs, which combine targeted antibodies with potent cytotoxins to selectively eliminate cancer cells. Her expertise also extends to discussions on biologics and T-cell engagers, signaling ongoing efforts to refine immune-based therapies in breast and other cancers.

Among other high-impact clinical presentations, Aditya Shreenivas, M.D., M.S., will report phase 3 trial results for Penpulimab, a humanized anti-PD-1 monoclonal antibody evaluated as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. These findings could redefine therapeutic options for this aggressive malignancy by improving survival and tolerability in diverse patient populations, reflecting City of Hope’s commitment to global oncology.

Research connecting fundamental biology to therapeutic resistance mechanisms will be illustrated by Kimya Karimi, a postdoctoral scholar investigating ways to overcome cell cycle inhibitor resistance in estrogen receptor-positive (ER+) breast cancer. By combining epigenetic and molecular analyses, this work aims to restore endocrine therapy efficacy, addressing a significant clinical challenge in breast cancer management.

The conference also spotlights the vital role of community engagement in translating scientific discoveries into health policy and patient outcomes. Kimlin Tam Ashing, Ph.D., will elaborate on frameworks for fostering community alliances and partnerships that promote equitable cancer care delivery. This integration of social science with biomedicine embodies City of Hope’s holistic vision of research impacting patients beyond the laboratory.

Highlighted poster sessions further reveal City of Hope’s versatile expertise. Senior research associate Jing Qian will present spatial transcriptomic data unmasking differences in tumor and immune microenvironments among high-grade serous ovarian cancers, providing insights into variable responses to checkpoint blockade immunotherapies. Similarly, hematology fellow Peter Zang will explore spatial proteomic distinctions in metastatic prostate cancer across ethnicities, informing biomarker development and personalized treatment strategies.

Lastly, cutting-edge computational approaches to cancer prognosis are represented by a team including postdoctoral fellow Sydney Grant and assistant professor Aritro Nath. Their application of survival-based variational autoencoders to integrate multimodal data advances predictive modeling of recurrence-free survival in breast cancer patients, potentially guiding individualized risk assessment and therapeutic planning.

City of Hope’s robust presence at AACR Annual Meeting 2025 exemplifies its unwavering commitment to integrating state-of-the-art technologies, clinical trials, and community-driven approaches. By harnessing artificial intelligence, multiomics, and immunotherapy research, their scientists and clinicians are shaping the future landscape of cancer care, striving to transform hope into tangible cures for patients worldwide.

Subject of Research: Advances in cancer research and treatment integrating artificial intelligence, multiomics, and immunotherapy at City of Hope.

Web References:

• City of Hope
• AACR Abstracts Portal

Image Credits: City of Hope

While mutations within a cell’s genetic structure have long been regarded as the primary instigators of cancer, this study shines a light on the multifaceted nature of tumorigenesis. By implicating chronic inflammation alongside genetic mutations, the findings convey a nuanced understanding of cancer that prompts a reevaluation of current prevention strategies. This research underscores the urgency to develop cancer prevention methods that address these biological triggers rather than merely targeting external carcinogens or lifestyle factors, such as avoiding known pollutants.

In the world of cancer research, one question has persisted: Can the presence of mutated cells alone lead to cancer? This study, recently published in the prestigious journal Cancer Discovery, offers a resounding answer. Through rigorous experimentation, the researchers aimed to dissect the relationship between cellular mutations and tumor development, a topic of interest that has remained elusive for many years.

Dr. Li articulates the conventional perspective of cancer prevention, which often focuses solely on minimizing exposure to carcinogens, such as smoking and environmental pollutants. However, her team’s insights advocate for a more holistic approach. According to Dr. Li, the biological mechanisms that foster tumor growth should be equally prioritized in cancer prevention efforts. The suggestion is that the development of cancer is not merely a consequence of genetic mutations but rather a complex interplay between genetic predisposition and environmental factors that drive inflammation.

A poignant example offered by Dr. Li relates to the observation that not all smokers develop lung cancer. What does this suggest about the multifactorial nature of cancer? She explains that while smoking serves as a vital initial carcinogenic trigger, it is often the co-occurrence of inflammatory processes that catalyzes tumor formation. Thus, to successfully mitigate cancer risk, it is crucial to understand and address the elements contributing to chronic inflammation.

Drawing from the team’s research, it is revealed that lifestyle factors such as obesity and a high-fat diet perpetuate chronic inflammation. Dr. Li stresses that the public should recognize this vital connection. While avoiding environmental hazards that cause mutations is necessary, it is equally crucial to steer clear of behaviors and conditions that instigate chronic inflammation, as they create an environment ripe for cancer development.

The research team’s experiments drew inspiration from foundational work conducted decades ago. By employing modern sequencing technologies, they were able to recreate an experiment from the 1950s, applying two progressive agents on skin tissue. The first agent induced significant genetic mutations, setting the stage for tumorous growth when followed by the introduction of the inflammatory agent. Remarkably, their findings suggested that even in the context of significant genetic mutation, these mutated cells may remain dormant until the right inflammatory trigger awakens them.

Integrating whole genome sequencing into their study confirmed the essential role of inflammation in advancing cancer development. Surprisingly, the exposure to both agents was necessary for tumor formation, emphasizing the nuanced orchestration of genetic and environmental factors in driving cancer. The revelations from this research assert that initial cellular mutations alone do not automatically lead to cancer; instead, these mutations exist like dormant seeds, waiting for an inflammatory catalyst to facilitate their growth into a malignant entity.

The ramifications of this study extend beyond mere academic curiosity; they could reshape the very landscape of cancer prevention. As Dr. Li points out, the implications of identifying the cellular mechanisms of tumor promotion could lead to the development of innovative strategies to thwart cancer before it has a chance to manifest. This proactive perspective urges the scientific community to pivot from reactive approaches to more anticipatory measures aimed at prevention.

Future research will delve deeper into understanding how inflammation alters the epigenome and the metabolic pathways that may reactivate latent mutated cells. By investigating how chronic inflammation modifies these critical biological processes, Dr. Li hopes to uncover groundbreaking insights that could revolutionize cancer prevention methodologies.

As the scientific community digests the findings revealed by this research, it remains evident that the quest to conquer cancer encompasses far more complexity than previously understood. Armed with new information regarding the relationship between chronic inflammation and tumor development, future directions in cancer research could illuminate pathways to more effective preventive strategies, ultimately leading to a significant reduction in cancer incidence across populations.

With this monumental study paving the way for future innovations in cancer prevention, the researchers at City of Hope have opened a new chapter in our understanding of cancer biology. Their commitment to unraveling the intricacies of tumor development fosters hope for the millions impacted by cancer, propelling the scientific community closer to comprehensive solutions that can combat this pervasive disease.

The revelations from Dr. Li’s team offer a crucial perspective on the intricate tapestry of cancer causation, asserting that preventing malignancies goes beyond simply targeting mutations. A multifaceted approach illuminating the pathways of inflammation holds significant promise for future breakthroughs, thereby reshaping public health strategies dedicated to cancer prevention.

As we look to the future, the message is clear: understanding tumor biology demands a holistic approach, weaving together genetics, environmental factors, and inflammation. Such insights not only inform research directions but also arm the public with knowledge essential for navigating their health journeys in an increasingly complex landscape of cancer risk factors.

Subject of Research: Animals
Article Title: Long term latency of highly mutated cells in normal mouse skin is reversed by exposure to tumor promoters and chronic tissue damage
News Publication Date: 13-Mar-2025
Web References: (Not available)
References: (Not available)
Image Credits: Credit: City of Hope

Keywords: Cancer research, Genome sequencing, Chronic inflammation, Tumor formation, Cancer prevention, Genetics, Cell biology