Creation and Development of Patient-Derived Organoids for Therapeutic Screening in Solid Cancer

Purpose of Review Clinical implementation of personalized cancer therapy necessitates translational cancer models that faithfully represent the molecular and cellular features of human cancer. Current patient-derived preclinical models, including cell line and xenograft models, are limited by incomplete recapitulation of parental tumor heterogeneity and long induction times, impeding their ability to directly inform clinical decision-making. Newly emerging patient-derived organoids (PDOs) of solid tumors retain the intra-tumoral heterogeneity lost in many preclinical models and mirror the therapeutic responsiveness of their parent tumors. Herein, we explore the origins and rationale for organoid cancer modeling, the creation of PDO models through an illustrative example of glioma organoids, and their downstream use in comprehensive drug screens to guide oncologic therapy selection. Recent Findings Cancer organoid models have been generated through numerous techniques, producing PDOs of brain, pancreatic, breast, and gastrointestinal cancer, among others. Recent evidence supports the creation of PDOs using a minimally processed approach, whereby manually parcellated tissue can produce viable organoids in the absence of tissue dissociation, an artificial extracellular matrix, and exogenous growth factors. Refinement of these models thus allows PDOs to serve as patient avatars, and early evidence demonstrates similar responses to chemotherapy and radiotherapy as the parent tumor. Summary The retention of key molecular, histopathologic, and phenotypic features of numerous human cancers offers compelling support for the use of PDOs as translational cancer models. Given the ability to rapidly create these models following tumor resection, PDOs can be used as platforms for personalized drug screens to guide the selection of oncologic therapies.