Following a special conference organised by the American Association for Cancer Research (AACR) "Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic" (11-14 February, 2016, New Orleans, USA), Heidi Ledford wrote in Nature News, that after more than 25 years of heavy use by researchers around the world, the US National Cancer Institute (NCI) has decided to retire the NCI-60, its panel of 60 human cancer cell lines grown in culture. In late spring of 2016, the institute will launch a rejuvenated repository of cancer models that are derived from fresh patient tumour samples and tagged with details about their clinical past.
Since 1990, industry and academic have screened more than 100,000 compounds using the NCI-60, in order to study the molecular details of cancers and find drugs to treat them. However, when the NCI-60 was established, researchers had a very different conception of cancer.
Like most other cancer cell lines, the NCI-60 have lived in an environment that differs radically from their native one. Over time, the cells have adapted to life in plastic petri dishes, altering their genetic make-up and behaviour. To replace the cultures, the NCI is turning to patient-derived tumour xenografts (PDXs), the models in which the tumours grow in an environment that, although not human, better mimics their native environment. The NCI will distribute cells from those PDXs, as well as data regarding each tumour’s genetic make-up and gene expression patterns, and the donor’s treatment history.
In addition, the institute will make cell lines from the samples for use in more detailed biochemical studies and drug screening. For some cell lines, the repository will also contain cultures of associated, non-cancerous cells called fibroblasts, to allow researchers to learn more about how these cells can influence a tumour’s response to treatment. The institute is also developing cell cultures and xenografts from tumour cells circulating in the blood. The team is about a third of the way to its initial goal of producing 1,000 models, but will probably only have about 75 models ready for distribution when the repository opens.
The NCI effort reflects a wider trend: several institutions have begun to develop repositories of PDX models. Sixteen European institutions together form the EurOPDX Consortium that boasts 1,500 PDXs. The Jackson Laboratory, a non-profit company has 450 PDXs, and another 100 in development. Many more reside in pharmaceutical companies: last year, the Novartis published a drug screen using 1,000 PDXs.
Mice bearing PDXs could serve as ‘avatars’ to allow physicians to screen for the most-effective treatment regimen. But the process of generating a PDX is often too slow to benefit the donor. Such models promise to capture the genetic complexity of human cancers better than can old cell cultures or genetically engineered mice, but PDXs also have shortcomings. Most are generated in mice that lack normal immune responses, to prevent the human cells from being rejected. Efforts are under way to engineer mice with aspects of the human immune system.
Despite their limitations, some researchers say they have already translated PDX results into clinical gains. Livio Trusolino of the University of Turin in Italy, and his colleagues mined their collection of 600 colorectal cancer PDXs. At the AACR meeting, Dr Trusolino discussed data showing that PDXs from these tumours respond better to a combination of drugs already available for the treatment of breast cancer.
The ACCR Conference was co-chaired by four distinguished researchers, among them two are members of the ESMO Translational Research and Personalised Medicine Working Group (TR and PM WG), in particular Dr Joan Seoane (VHIO, Barcelona, Spain), who is an EACR representative in the ESMO TR and PM WG, and Dr Gail Eckhardt (University of Colorado Cancer Center, Aurora, Colorado, USA), an ex member of the ESMO TR and PM WG, who committed in the past a special video on PDX models within ESMO initiative to educate clinicians in this emerging field.