Functional precision cancer medicine: drug sensitivity screening enabled by cell culture models

Functional precision medicine is a new, emerging area that can guide cancer treatment by capturing information from direct perturbations of tumor-derived, living cells, such as by drug sensitivity screening. Precision cancer medicine as currently implemented in clinical practice has been driven by genomics, and current molecular tumor boards rely extensively on genomic characterization to advise on therapeutic interventions. However, genomic biomarkers can only guide treatment decisions for a fraction of the patients. In this review we provide an overview of the current state of functional precision medicine, highlight advances for drug-sensitivity screening enabled by cell culture models, and discuss how artificial intelligence (AI) can be coupled to functional precision medicine to guide patient stratification. Functional precision medicine provides strategies to support clinical decisions on personalized treatment of cancer patients by using functional tests on live patient cells, for example, by testing cell viability after exposure to drugs.For hematological cancers, the methods and test platforms have matured to a stage where drug sensitivity testing is being implemented in prospective clinical trials as a stratification tool to complement genomic and transcriptomic information.For solid tumors, increasing evidence from co-clinical trials using a breadth of test systems to assess the drug sensitivity of patient cells coupled to clinical outcome allows validation of the tests.The field of functional testing in precision cancer medicine is thus moving towards its implementation as a diagnostic method to provide more information to molecular tumor boards.