Unmasking prostate cancer risk factors leveraging organoid technology

Organoid technology is rapidly refining our understanding of organ development, physiology, and disease. The generation of patient-derived organoid cultures is paving the way for effective personalized treatments, defined based on specific genetic and molecular criteria. Moreover, the possibility of testing in vitro the response of tumor cells to the most appropriate therapeutic regimes helps to anticipate the emergence of resistance, to define the molecular mechanisms involved and, in turn, to tailor treatment through a bed-to-bench-to-bed co-clinical strategy. In addition, the creation of organoid biobank provides an opportunity to reduce the reliance on animal models, while expanding the scale and relevance of patient/human material derived analyses, ultimately accelerating the preclinical-to-clinical workflow. Prostate cancer (PCa) is one of the most common cancers in men world-wide, second only to lung cancer. Although not particularly aggressive, PCa lethality remains a clinical issue. The paucity of innovative molecular targeted therapies and the ineligibility for immunological strategies limit the clinical intervention to mainly surgery or radiotherapy for organ confined tumors, and systemic hormone therapy in the case of advanced metastatic disease. Initially effective in most patients, tumor almost inevitably relapses with palliative care remaining the only option. In this review we provide a historical and conceptual overview of organoid technology, we discuss its application in prostate cancer and outline future prospective for the development of an organoid based platform aimed at risk stratification, risk factor studies, therapeutic prediction, and personalized medicine.