Patient Derived Organoids (PDOs), Extracellular Matrix (ECM), Tumor Microenvironment (TME) and Drug Screening: State of the Art and Clinical Implications of Ovarian Cancer Organoids in the Era of Precision Medicine

SIMPLE SUMMARY: Ovarian cancer (OC) has the highest mortality rate of any gynecological malignancy due to the advanced-stage diagnosis, high therapeutic resistance, high recurrence rate, and lack of targeted personalized treatments. This requires the development of preclinical models that can mimic the histological, molecular, and pathophysiological characteristics of various OC subtypes according to patient characteristics. In this scenario, patient-derived organoids represent an emerging model (PDOs). PDOs are 3D dynamic tumor models that can be grown successfully from patient-derived ovarian tumor tissue, ascites, or pleural effusion. This model recapitulates the heterogeneity of OC and allows for drug screening as well as the development of new target therapies. The purpose of this study is to provide information on PDOs and the critical role of the extracellular matrix (ECM) and the tumor microenvironment (TME) in their development to implement precision medicine in patients with patients with patients with ovarian cancer. ABSTRACT: Ovarian cancer (OC) has the highest mortality rate of all gynecological malignancies due to the high prevalence of advanced stages of diagnosis and the high rate of recurrence. Furthermore, the heterogeneity of OC tumors contributes to the rapid development of resistance to conventional chemotherapy. In recent years, in order to overcome these problems, targeted therapies have been introduced in various types of tumors, including gynecological cancer. However, the lack of predictive biomarkers showing different clinical benefits limits the effectiveness of these therapies. This requires the development of preclinical models that can replicate the histological and molecular characteristics of OC subtypes. In this scenario, organoids become an important preclinical model for personalized medicine. In fact, patient-derived organoids (PDO) recapture tumor heterogeneity with the possibility of performing drug screening. However, to best reproduce the patient’s characteristics, it is necessary to develop a specific extracellular matrix (ECM) and introduce a tumor microenvironment (TME), which both represent an actual object of study to improve drug screening, particularly when used in targeted therapy and immunotherapy to guide therapeutic decisions. In this review, we summarize the current state of the art for the screening of PDOs, ECM, TME, and drugs in the setting of OC, as well as discussing the clinical implications and future perspectives for the research of OC organoids.