Breakthrough Research Illuminates New Frontiers in Cancer Biology, Neurodegeneration, and Immunology at City of Hope
In a remarkable series of scientific advancements, researchers at the City of Hope cancer research and treatment center have unveiled critical insights spanning RNA modifications in cancer, innovative immunotherapy timing in lung cancer, stem cell therapy for neurological disorders, and groundbreaking discoveries in immune regulation. These cutting-edge studies not only deepen our understanding of complex disease mechanisms but also open promising new avenues for therapeutic intervention.
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.
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Image Credits: City of Hope / Yanhong Shi Lab
Keywords: Cancer, Lung cancer, Stem cell research
