The models were developed through the Human Cancer Models Initiative, an international effort involving the National Cancer Institute, Cancer Research UK, the Wellcome Sanger Institute and Hubrecht Organoid Technology. The initiative aims to create 1,000 patient-derived models that accurately reproduce the biology of human tumors in laboratory systems. Approximately 2,800 patients from the United States, the United Kingdom, Italy and the Netherlands consented to provide tumor tissue and associated clinical information for the project.

Unlike many traditional laboratory cancer models, the new collection was designed to preserve the biological features of the tumors from which they originated. Patient-derived models can include three-dimensional organoids and spheroids, as well as two-dimensional cell lines. These systems are grown under conditions tailored to the specific cancer type, helping maintain the genetic, molecular and cellular characteristics of the original tumor. The models that passed rigorous quality-control procedures were subjected to standardized genomic sequencing and molecular profiling.

This validation process addresses a major weakness of earlier cancer models. Cells grown in laboratories can gradually acquire genetic or biological changes, a phenomenon often described as “drift,” which may make them increasingly different from the patient’s tumor. Such changes can undermine experiments designed to predict how a cancer will respond to a drug or how a genetic alteration contributes to disease. The HCMI models were selected for their ability to remain faithful to the original samples and to retain stable biological behavior over extended periods.

The collection includes cancers affecting both adults and children, with examples ranging from colorectal, pancreatic, lung and brain cancers to much rarer malignancies. More than 20 percent of the models represent rare cancer types, some of which previously had only one or two experimental models available to researchers worldwide. Expanding representation of these diseases could be particularly important because rare cancers often lack the large patient populations and research infrastructure that support studies of more common tumors.

Clinical context is another defining feature of the resource. Among the models are 168 derived from patients who had already received treatment, including immunotherapy, targeted therapy, chemotherapy and radiotherapy. Another 318 models were generated from samples collected before treatment. Linking the laboratory models to treatment history and patient outcomes may allow researchers to investigate why some tumors resist therapy, identify molecular features associated with response and test potential combinations of drugs in systems that reflect real-world disease.

The models and their associated data are being distributed through the American Type Culture Collection. Researchers will be able to access not only the physical biological materials but also information such as genomic sequencing results, clinical annotations and molecular measurements generated using consistent methods. According to the investigators, this unified structure is essential because it allows findings from different laboratories to be compared more reliably than when researchers use unrelated models created under different conditions.

The resource has already contributed to the expansion of the Cancer Dependency Map, or DepMap, a large-scale effort managed by the Broad Institute that uses CRISPR gene-editing technology to identify genes on which cancer cells depend. By incorporating the HCMI models, investigators have broadened DepMap’s coverage of genetic and molecular cancer subtypes. The new models also include gene-expression patterns and cellular states that were not consistently represented in earlier patient-derived systems, potentially revealing vulnerabilities that had remained invisible in previous screens.

The scientific importance of the collection extends beyond the immediate experiments it enables. With hundreds of carefully characterized models connected to clinical and genomic data, researchers can perform large-scale studies of tumor evolution, drug resistance, cancer dependencies and interactions between genetic alterations. The dataset may also provide valuable training material for computational tools and artificial-intelligence systems designed to predict treatment response or prioritize drug targets. The investigators describe the release as a major change in the experimental infrastructure available to cancer biology, particularly because it combines standardized models with deep patient-level information.

The Nature study, titled “A Compendium of Next-Generation Patient-Derived Models for Diverse Cancers,” was led by investigators including Keith Ligon of Dana-Farber Cancer Institute, Jesse Boehm of the Massachusetts Institute of Technology, Mathew Garnett of the Wellcome Sanger Institute, David Tuveson of Cold Spring Harbor Laboratory and collaborators from institutions across the United States and Europe. The HCMI was funded primarily by the National Cancer Institute and the Wellcome Trust. By making the models broadly accessible, the initiative aims to give researchers the experimental systems needed to translate cancer genome discoveries into new therapies more quickly.

Subject of Research:
Next-generation patient-derived cancer models, including organoids, spheroids and cell lines, for studying tumor biology, treatment response and therapeutic vulnerabilities.

Article Title:
A Compendium of Next-Generation Patient-Derived Models for Diverse Cancers

Web References:
https://www.atcc.org/hcmi
https://depmap.org/portal/
https://doi.org/10.1038/s41586-026-10806-y

References:
Nature article, DOI: 10.1038/s41586-026-10806-y

Keywords:
Cancer research, patient-derived models, organoids, cancer biology, precision medicine, drug discovery, tumor modeling, Cancer Dependency Map, CRISPR screening, genomics, rare cancers, Dana-Farber Cancer Institute, Human Cancer Models Initiative

Mount Sinai’s multifaceted research portfolio reflects its unwavering commitment to confronting some of oncology’s most challenging frontiers. This year’s presentations span a diverse spectrum of cancer specialties, including hematologic malignancies, thoracic oncology, urothelial cancer, gynecologic oncology, translational science, and cancer care delivery. The breadth and depth of these contributions underscore Mount Sinai’s role as a leader in developing sophisticated, personalized approaches to cancer therapy—approaches that marry benchside discoveries with bedside applications.

Among the highlights is a highly anticipated late-breaking oral presentation by Dr. John Mascarenhas, Professor of Medicine and Director of the Center of Excellence for Blood Cancer and Myeloid Disorders at Mount Sinai Tisch Cancer Center. Dr. Mascarenhas will reveal pivotal results from the phase 3 SENTRY trial, which evaluates the combination of selinexor and ruxolitinib in patients with JAK inhibitor-naïve myelofibrosis. This trial explores a novel therapeutic strategy designed to inhibit aberrant signaling pathways responsible for the proliferation of malignant hematopoietic cells. Scheduled for June 2 during the Hematologic Malignancies oral abstract session, these findings hold significant promise for patients with this debilitating myeloproliferative disorder.

In the arena of thoracic oncology, Mount Sinai investigators are advancing the frontier of immunotherapy through research on HLX43, an anti-PD-L1 antibody-drug conjugate. This Rapid Oral Abstract Session presentation examines HLX43’s efficacy and safety in patients with advanced non-small cell lung cancer (NSCLC), delving into its potential to harness immune checkpoint inhibition to augment tumor targeting and destruction. Antibody-drug conjugates represent a cutting-edge modality designed to deliver cytotoxic agents directly to cancer cells while minimizing off-target effects.

Beyond these oral sessions, Mount Sinai’s robust research pipeline includes a variety of poster presentations tackling pressing questions across multiple cancer types. Studies investigating macrophage polarization in metastatic urothelial cancer highlight the CXCL9:SPP1 ratio as a predictive biomarker for response to pembrolizumab and enfortumab vedotin combination therapies. This work provides new insights into tumor microenvironment dynamics, emphasizing the role of immune cell modulation in therapeutic outcomes.

Additional poster research assesses national trends in immunotherapy use among patients with metastatic head and neck squamous cell carcinoma, employing data from the National Cancer Database. These epidemiological studies reveal critical patterns in end-of-life treatment, ultimately guiding more compassionate and effective care strategies. Further work from Mount Sinai evaluates overall survival patterns in mucosal melanoma patients before and after the widespread adoption of PD-1 based checkpoint inhibitors, shedding light on the transformative impact of immunotherapy in rare and aggressive malignancies.

Investigations into relapsed/refractory multiple myeloma feature comparative analyses of belantamab mafodotin added to bortezomib and dexamethasone versus standard of care. These studies are instrumental in refining therapeutic algorithms and optimizing patient outcomes in a disease known for its complexity and heterogeneity. On the biomarker frontier, research on Keratin 19 (KRT19) as a circulating tumor biomarker offers a promising avenue for non-invasive disease monitoring and treatment guidance in urothelial carcinoma.

Cutting-edge molecular diagnostics are also exemplified by studies evaluating pre-cystectomy circulating tumor DNA (ctDNA) levels to differentiate patients with surgically curable disease from those harboring occult micrometastatic progression. These advances could pave the way for precision staging and personalized adjuvant therapy strategies, revolutionizing bladder cancer management.

Mount Sinai clinicians continue to pioneer novel immunomodulatory therapeutic concepts, such as trials investigating tolododekin alfa (ANK-101) in combination with anti-PD-1/PD-L1 antibodies in advanced NSCLC. This phase 1b study aims to potentiate immune responses by modulating cytokine environments, potentially overcoming resistance mechanisms inherent to checkpoint blockade monotherapy.

Urothelial carcinoma research remains a central focus, exemplified by multiple studies including the CheckMate-901 trial examining biomarker profiles associated with durable disease control in advanced disease treated with nivolumab plus ipilimumab. Similarly, the TROPION-Urothelial03 trial compares datopotamab deruxtecan plus chemotherapy versus the current standard of care in heavily pretreated patients, illustrating Mount Sinai’s commitment to improving outcomes in this challenging cancer subtype.

In the realm of myelofibrosis, the MY-PAC study investigates treatment patterns and clinical outcomes among patients treated with pacritinib, especially those with higher platelet counts. This research helps elucidate safety and efficacy profiles critical to managing this patient population. Additionally, updates on IMPROVEMF, a phase 1b trial combining imetelstat and ruxolitinib in intermediate and high-risk myelofibrosis, signify ongoing efforts to enhance therapeutic benefits and address unmet clinical needs.

The Mount Sinai Tisch Cancer Center, a National Cancer Institute-designated Comprehensive Cancer Center, remains at the forefront of integrating basic, clinical, and population health research. With a strategic focus on tumor types prevalent in its catchment area—including liver, prostate, breast, bladder, and lung cancers—Mount Sinai is uniquely positioned to translate cutting-edge research into meaningful advancements in patient care. Its extensive network, encompassing seven hospitals and over 400 physician practices, allows Mount Sinai to deliver multidisciplinary expertise alongside a growing portfolio of innovative clinical trials.

Notably, the construction of the soon-to-be-completed Mount Sinai Tisch Cancer Hospital will further augment the center’s capacity for pioneering research and patient-centered care, equipped with state-of-the-art facilities designed to accelerate translational research and clinical innovation. As these advancements unfold, Mount Sinai continues to steer oncology toward a future where personalized medicine transforms prognosis and quality of life for patients worldwide.

For more information about the ASCO Annual Meeting and to explore the full breadth of research presented by Mount Sinai, visit the official ASCO Annual Meeting website.

Subject of Research: Cancer research, including hematologic malignancies, thoracic oncology, urothelial cancer, gynecologic oncology, immunotherapy, biomarker-driven approaches, multiple myeloma, and myelofibrosis.

Article Title: Mount Sinai Tisch Cancer Center Unveils Breakthrough Cancer Research at ASCO 2026 Annual Meeting

News Publication Date: May 27, 2026

Web References:

• https://www.asco.org/annual-meeting
• https://www.asco.org/abstracts-presentations/262643
• https://www.asco.org/abstracts-presentations/263356
• https://www.asco.org/abstracts-presentations/261730
• https://www.asco.org/abstracts-presentations/267968
• https://www.asco.org/abstracts-presentations/260701
• https://www.asco.org/abstracts-presentations/262647
• https://www.asco.org/abstracts-presentations/266782
• https://www.asco.org/abstracts-presentations/262606
• https://www.asco.org/abstracts-presentations/266904
• https://www.asco.org/abstracts-presentations/267846
• https://www.asco.org/abstracts-presentations/266659

Keywords: Myelofibrosis, hematologic malignancies, antibody-drug conjugates, immunotherapy, non-small cell lung cancer, urothelial carcinoma, circulating tumor DNA, biomarker-driven treatment, multiple myeloma, PD-1 checkpoint inhibitors, cancer clinical trials, personalized cancer therapy.

Comprehensive genomic profiling, a cutting-edge approach introduced in oncology to analyze a broad spectrum of cancer-driving genes simultaneously, has been instrumental in personalizing treatment strategies. However, the exponential growth of detected genetic variants with unclear clinical significance—the VUS—presents a formidable barrier. These variants cloud clinical decision-making because their effects on gene function and cancer progression are poorly understood. Hiroshima University’s novel framework addresses this bottleneck, enabling clinicians and researchers to distinguish potential disease-causing variants warranting further functional investigation from those less likely to be clinically relevant.

The team focused this innovative analytical framework on the well-characterized BRCA1 and BRCA2 genes, notorious for their roles in hereditary breast and ovarian cancer syndromes. These genes serve as an ideal model system due to the wealth of existing clinical data linking specific mutations to cancer risk. Utilizing real-world CGP data from over 2,100 tests conducted across 13 Japanese institutions, the researchers cataloged 526 BRCA1/2 variants, of which a significant majority represented VUS. This striking prevalence emphasizes the urgent need for systematic strategies like the one developed here to navigate the sea of genomic ambiguity.

At the heart of the framework lies an integrative computational approach leveraging ten sophisticated in silico prediction tools. These bioinformatics algorithms assess the potential impact of each genetic variant on protein structure, function, and RNA splicing efficiency. By synthesizing these predictive data, the framework prioritizes a subset of VUS most likely to perturb BRCA1/2 function, thereby honing the focus of subsequent laboratory-based functional assays. This pipeline marries state-of-the-art computational biology with clinical genomics, birthing a model of precision that could revolutionize how CGP results are interpreted globally.

A compelling case study highlights the clinical relevance of this approach. One patient exhibiting an exceptional therapeutic response to platinum-based chemotherapy—despite a generally poor prognosis and metastasis across multiple organs—was found to harbor the BRCA2:c.67G>C variant. Functional analyses validated that this variant disrupts normal splicing of the BRCA2 gene, leading to exon skipping and a consequent frameshift, effectively incapacitating the gene’s tumor suppressor function. This mechanistic insight not only classified BRCA2:c.67G>C as pathogenic but also helped explain the patient’s remarkable sensitivity to treatment.

Such discoveries underscore the potential clinical transformations enabled by the prioritization framework. By more accurately identifying pathogenic VUS, oncologists can better stratify patients for targeted therapies, improve prognostication, and refine genetic counseling protocols. The strategy’s scalability suggests it could be adapted beyond BRCA genes to other hereditary cancer syndromes and inherited disorders, expanding the reach of precise genomic medicine.

Since Japan’s introduction of CGP into oncological care in 2019, over 100,000 cancer patients have undergone such genomic testing, emphasizing the urgent need for tools that can sift through vast, complex datasets. This framework elegantly addresses this demand by offering a methodical, data-driven lens through which to view the bewildering array of VUS routinely detected.

Leading this transformative work, Dr. Hiroaki Niitsu of Hiroshima University Hospital articulates the motivation, noting how clinical anomalies—such as the patient with extraordinary remission—sparked the drive for a more nuanced understanding of VUS implications. This synergy between clinical observation and genomic data interpretation exemplifies how modern precision oncology marries bedside insights with bench innovations.

By combining comprehensive genomic data with rigorous computational modeling, this study illuminates a pathway for researchers and clinicians alike to confront the twin challenges of variant ambiguity and treatment personalization. It points toward a future where VUS are no longer enigmatic stumbling blocks but targeted clues unlocking the mysteries of cancer biology and therapy responsiveness.

Moreover, the study invites the oncology community to rethink traditional variant classification. By incorporating multifaceted, multilayered in silico analyses into routine CGP interpretation, the authors chart an evolution from reliance on binary pathogenic/benign labels toward a continuum of variant characterization informed by functional potential and clinical context.

In conclusion, Hiroshima University’s prioritization framework marks a significant leap toward resolving one of precision oncology’s most pressing puzzles: turning uncertain genomic signals into actionable clinical knowledge. This integration of bioinformatics, genetics, and clinical insight promises to enhance treatment efficacy, patient outcomes, and perhaps most importantly, the future resilience of cancer care against the challenges posed by genomic complexity.

The study was published in the European Journal of Human Genetics on March 2, 2026, co-authored by a multidisciplinary team spanning Hiroshima University Hospital, Hiroshima University, and Hiroshima Prefectural Hospital. Supported by dedicated university subsidies and research grants, this work exemplifies the power of collaborative scientific inquiry in pushing the boundaries of personalized medicine.

Subject of Research: People

Article Title: A prioritization framework for BRCA1/2 variants of uncertain significance identified by comprehensive genomic profiling

News Publication Date: 2-Mar-2026

Web References:
European Journal of Human Genetics Article
DOI Link

References:
Nakahara et al., European Journal of Human Genetics, March 3, 2026.

Image Credits:
Nakahara et al., European Journal of Human Genetics, March 3, 2026

Keywords:
Comprehensive Genomic Profiling, Variants of Uncertain Significance, BRCA1, BRCA2, Precision Oncology, Bioinformatics, Cancer Genomics, Functional Genomics, Genetic Variant Prioritization, Hereditary Breast and Ovarian Cancer, In Silico Prediction, Genomic Medicine