New patient-derived cancer models unveiled for global research

/ in E-News

An international consortium has published details of a large collection of next-generation, patient-derived cancer models in Nature, giving laboratories worldwide new tools with which to study tumour biology and screen for therapeutic targets.

A total of 665 next-generation cancer models derived from patient tumours have been made available to researchers globally, according to a study published in Nature on 5 August 2026. The paper, led by investigators at Dana-Farber Cancer Institute, the Broad Institute and MIT’s Koch Institute, describes models representing 25 distinct cancer types. The collection represents the culmination of a ten-year international effort known as the Human Cancer Models Initiative (HCMI), funded primarily by the US National Cancer Institute and the Wellcome Trust, with additional partners including Cancer Research UK, the Wellcome Sanger Institute and the Hubrecht Organoid Technology foundation.

Filling gaps left by existing collections

The HCMI was established in 2016, following completion of the Cancer Genome Atlas, which sequenced tumour samples from thousands of patients and showed that the roughly 1,000 patient-derived cell lines then available did not adequately capture the genetic range of tumours seen in the clinic.

“We realized that a thousand wasn’t enough, that the international community needed to invest in many more thousands to represent all cancers, all genotypes, all ethnicities,” said Jesse Boehm, a research scientist at the Koch Institute and one of the study’s senior authors. “Most existing models come from European and Southeast Asian patients, and many rare cancers are missing.”

From tumour sample to validated model

Between 2016 and 2021, 2,780 patients across hospitals in the United States, the United Kingdom, Italy and the Netherlands consented to donate tumour tissue for the initiative; tissue from 637 of these patients was ultimately used to generate the 665 validated models, a process that could take up to a year per model. Most were established as organoids (519 models, 78%) – three-dimensional cell cultures embedded in a gel-like scaffold that can survive indefinitely and more closely mimic native tissue architecture than the single-layer cell lines developed since the 1950s. The remainder comprise 3D spheroid cultures (37 models, 6%) and conventional two-dimensional cell lines (109 models, 16%), covering both adult and paediatric cancers.

Some 153 models (23%) represent rare cancer types, for which very few models previously existed, and 71 derive from donors of predominantly non-European ancestry. The collection includes 168 models derived from samples taken after patients had already received treatment – among them immunotherapy, targeted therapy, chemotherapy and radiotherapy – and 318 from treatment-naive samples.

Each model was validated against its originating tumour: in a direct comparison of 421 matched tumour-model pairs, the authors report genetic concordance of 97.8% and epigenetic concordance of 95%. Extensive clinical data, including treatment history and outcomes, were compiled for 78% of models (522 of 665). All models have been deposited with the American Type Culture Collection ( https://www.atcc.org ), through which researchers can access them.

“A resource of this scale depends on the kind of systematic effort that often happens behind the scenes,” said Mushriq Al-Jazrawe, scientific director of the High Throughput Sciences platform at the Koch Institute and a lead author of the study.

Mapping vulnerabilities

In a companion Nature paper, investigators at the Broad Institute reported profiling more than 300 of the new models using genome and RNA sequencing, and more than 100 using CRISPR loss-of-function screens, to identify molecular vulnerabilities that could be targeted by new drugs.

These data have been incorporated into the Cancer Dependency Map (DepMap) ( https://shorturl.at/kziOk ), which now holds information on more than 2,000 cancer models. A further companion paper from the Wellcome Sanger Institute describes the characterisation of an additional 256 organoids generated through the HCMI.

Keith Ligon, founding director of Dana-Farber’s Center for Patient Derived Models, said the resource “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.” He added that the models “meet strict criteria to be faithful to the original biology, while prior generations of models sometimes went through big biological changes over time that were not natural.”

Looking ahead

Although the formal HCMI programme is now winding down, those involved say the underlying work will continue. “We now have about 2,000, but if we really want to represent all humans with cancer in our preclinical research, more work is needed. We have to invite patients to donate tissue to make research tools that the whole world can use,” said Boehm. “I think this will hopefully be not the end, but the beginning.”

Reference:
ElHarouni, D., Al-Jazrawe, M., Choi, S., et al. (2026). A compendium of next-generation patient-derived models for diverse cancers. Nature. https://shorturl.at/Cu8wI