MIT unveils 600+ cancer models

MIT and partner institutions said on August 5 that researchers can now access one of the largest new public sets of patient-derived cancer models, a collection built to give labs more realistic systems for studying tumors and testing drugs. The release includes 665 models spanning 25 cancer types and draws on tumor samples from 2,780 donors, according to MIT and the National Cancer Institute’s Human Cancer Models Initiative. The project was published August 5 in Nature, alongside a companion paper showing how the new 3D models can expand CRISPR-based cancer dependency mapping beyond standard cell lines. MIT said the work was led by researchers at the Koch Institute, the Broad Institute, Dana-Farber Cancer Institute, the National Cancer Institute and other institutions. ### Why did researchers build hundreds of new cancer models in the first place? (news.mit.edu) The Human Cancer Models Initiative was launched in 2016 after researchers concluded that the roughly 1,000 patient-derived cancer cell lines then in common use did not capture the diversity seen in tumor-genome data. Jesse Boehm, a research scientist at MIT’s Koch Institute and a senior author, said scientists had identified many possible cancer targets but still needed lab systems that could validate them and support drug-discovery work. (news.mit.edu) Nature’s summary of the main paper said the resource was designed as a “compendium” of next-generation patient-derived models for diverse cancers. The National Cancer Institute says the broader HCMI program aims to create up to 1,000 patient-derived models, including organoids, neurospheres and other systems, as a community resource. ### What exactly is in the new collection? The main HCMI paper reports 665 patient-derived models generated from 2,780 donors across 25 cancer types, with integrated whole-genome, exome, methylome and transcriptome analyses. (news.mit.edu) The dataset includes 522 models with comprehensive clinical data, 153 models of rare cancers and 71 models from participants with non-European ancestry, according to the National Cancer Institute’s data portal. (nature.com) MIT said most of the new models were created by converting tumor cells into organoids, or 3D cultures that can survive indefinitely while preserving key genetic and molecular features of the original tumors. The models are derived directly from patient tumors rather than adapted long-term laboratory lines. ### Why are organoids and other patient-derived models getting so much attention? (gdc.cancer.gov) Nature and other recent reviews describe patient-derived organoids and explants as more physiologically relevant than many traditional 2D systems because they preserve more of the heterogeneity seen in human tumors. Researchers use those models to study tumor biology, compare drug responses and, in some settings, support precision-medicine research. (news.mit.edu) MIT said the new collection is intended to help researchers identify drug targets and test potential treatments across a wider range of cancers, including rarer tumor types that have been underrepresented in existing model libraries. Boehm said earlier model collections were missing many rare cancers and overrepresented patients of European and Southeast Asian ancestry. (cell.com) ### How well do these new models match the tumors they came from? ATCC, which distributes HCMI models, said a Nature study found high agreement between patient tumors and matched organoid models in genetic, epigenetic and transcriptional profiles. ATCC cited 97.8% genetic concordance, 95% epigenetic concordance and 92% transcriptional similarity across 421 tumor-model pairs. (news.mit.edu) Those figures come from ATCC’s summary of the peer-reviewed paper, and they address one of the central questions in cancer-model research: whether a lab-grown system still resembles the patient tumor closely enough to be useful in translational experiments. Recent reviews in Cell and Nature have described that fidelity issue as a key test for organoid and explant platforms. (atcc.org) ### Where can researchers get the models, and what comes next? The National Cancer Institute says HCMI-developed models and related clinical and molecular data are available as a community resource through the initiative’s program pages and associated repositories. MIT said the cells are available to cancer researchers around the world, and the August 5 Nature package includes the core resource paper plus the dependency-map companion study. (cancer.gov) (atcc.org)