Human Cancer Model Initiative Publishes 665 Next-Generation Patient-Derived Organoid Models Spanning 25 Cancer Types
核心洞察
The NCI-led Human Cancer Model Initiative published 665 validated patient-derived organoid models covering 25 cancer types in Nature, doubling the number of in vitro models available globally.
The CSHL-Northwell Health consortium contributed over 150 organoid models, including rare and underrepresented cancer subtypes such as endometrial and pediatric cancers.
Each model is annotated with comprehensive clinical data, treatment history, and advanced molecular profiles including DNA/RNA sequencing and epigenetic data.
A decade-long international effort to build next-generation patient-derived cancer models has reached a major milestone. The National Cancer Institute's Human Cancer Model Initiative (HCMI) has published a compendium of 665 organoid and cell-line models representing 25 types of cancer, now available to researchers worldwide through the American Type Culture Collection. The results, published in Nature, represent the largest single release of validated, clinically annotated patient-derived cancer models ever made public.
"This effort has created some of the most advanced and valuable patient-derived cancer models available for research today," said David Tuveson, Director of Cold Spring Harbor Laboratory (搜索)'s NCI-designated Cancer Center. "These organoids more closely reflect the biology of a patient's tumor, providing researchers with powerful tools to accelerate discovery and develop more personalized treatment strategies."
The CSHL-Northwell Health consortium, one of the largest international teams within HCMI, contributed more than 150 organoid models spanning pancreatic, breast, endometrial, colorectal, bladder, ovarian, head and neck, and lung cancers. The consortium also included leadership from the University of Verona in Italy and the Hubrecht Institute in the Netherlands, with organoid pioneer Hans Clevers among the collaborators.
A Resource Built for Rigor and Diversity
Launched in 2017, HCMI set out to generate a thousand three-dimensional cancer organoid culture systems—clusters of cells that accurately recapitulate actual tumors, enabling researchers to study both tumor biology and therapeutic response in a petri dish. CSHL served as an instructional site offering courses in organoid development and established a robust cancer hotspot sequencing–based quality control process at its Genome Center.
According to the Nature paper, the resource provides 522 models with comprehensive clinical data, 153 models of rare cancers, and 71 models from participants with non-European ancestry. Priya Sridevi, CSHL's HCMI lead program manager, emphasized that the repository includes matched tissue material from original tumors along with complete clinical information linked to each sample, plus advanced molecular profiles such as DNA and RNA sequences and transcriptomic and epigenetic data.
"Traditional cancer cell lines are not very representative of patient tumors, and patient-derived xenograft mouse models can be difficult to create and are very expensive," Sridevi explained. "Organoids are more representative, expandable, and cryo-preservable, enabling studies of cancer therapies to occur in a petri dish."
The collection includes 168 models from patients who had already received treatment—including immunotherapy, targeted therapy, chemotherapy, and radiotherapy—and 318 models from treatment-naïve samples. While most organoids were derived from adult donors, 43 were created from pediatric or adolescent donors, and 23 percent of successful models represent rare cancer types.
Closing Gaps in Underrepresented Cancers
CSHL Assistant Professor Semir Beyaz highlighted the initiative's impact on women's health research. "There is a big gap in women's health generally, but an even bigger gap in uterine and gynecological research, and we developed robust and high-fidelity endometrial cancer (搜索) models, including models from rare but aggressive subtypes and underrepresented groups," Beyaz said. "This is a very good step toward precision medicine."
The models have already demonstrated their utility beyond the initial compendium. CSHL Professor David Spector, who assisted in developing primary and metastatic breast cancer (搜索) organoids, noted that they enable faster drug screens. "The ultimate goal is to use organoids as a means of testing drugs to determine the best combination for a particular tumor and eventually feed that information to the oncologist," Spector said.
Expanding the Cancer Dependency Map
In a companion effort, researchers used the HCMI organoids to expand the Cancer Dependency Map (DepMap), a Broad Institute-managed resource that uses CRISPR technology to identify cancer vulnerabilities. The inclusion of next-generation models enabled DepMap to cover new genetic and molecular subtypes and study gene expression and cell states not reliably present in earlier patient-derived models.
"This effort doubles the number of in vitro models available for people to use and includes some very rare cancer types for which there were just one or two prior models available in the entire scientific community," said Keith Ligon, MD, PhD, founding director of Dana-Farber's Center for Patient Derived Models and co-senior author of the study. "This is likely to be everyone on the team's most important contribution to cancer biology in their career because the resulting resource enables new research at such a large scale and for many years into the future."
From Bench to Bedside
Northwell Health, which provides cancer care to more than 19,000 patients annually, was central to securing patient samples and building the pipeline between clinical care and research. "The success of the Human Cancer Model Initiative depended on seamless coordination between our Cancer Institute clinical teams, the Northwell Health Biospecimen Repository, and CSHL research partners," said James M. Crawford, Professor of Pathology and Laboratory Medicine at Northwell.
Richard Barakat, Physician-in-Chief and Executive Director of Cancer Services and Research at Northwell Health, underscored the patient-centered foundation of the work: "By working closely with the exceptional teams at Northwell, Cold Spring Harbor and our collaborators worldwide, every breakthrough we achieve in the lab brings us one step closer to transforming the lives of the patients we serve."
Professor Vincenzo Corbo, whose team at the ARC-Net Centre for Applied Research on Cancer at the University of Verona generated and distributed more than 70 pancreatic and colorectal cancer (搜索) models, said that seeing external researchers actively using the distributed models "is the ultimate validation of the project's impact."
The HCMI was funded primarily by the National Cancer Institute and the Wellcome Trust, with additional collaboration from Cancer Research UK, Wellcome Sanger Institute, and the foundation Hubrecht Organoid Technology. Approximately 2,800 patients from the United States, United Kingdom, Italy, and the Netherlands consented to contribute tissue and data.
"These new models and resources together represent a sea change advance in the tools available to the world, so we have what we need to fight cancer," Ligon said. "They will be essential for generating the deep data needed for AI to help us unlock new treatments and break down barriers to rapidly help patients."