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
by
, , , , , and
Giulia Spagnol
1,†
,
Francesca Sensi
2,3,†,
Orazio De Tommasi
1,
Matteo Marchetti
1,
Giulio Bonaldo
1,
Livia Xhindoli
1,
Marco Noventa
1, 
Marco Agostini
3,4,
Roberto Tozzi
1 and
Carlo Saccardi
1,* 1
Department of Women and Children’s Health, Clinic of Gynecology and Obstetrics, University of Padua, 35100 Padua, Italy
2
Department of Women and Children’s Health, University of Padua, 35100 Padua, Italy
3
Fondazione Istituto di Ricerca Pediatrica Città della Speranza, 35129 Padua, Italy
4
General Surgery 3, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, 35100 Padua, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2023, 15(7), 2059; https://doi.org/10.3390/cancers15072059
Submission received: 2 March 2023
/
Revised: 27 March 2023
/
Accepted: 27 March 2023
/
Published: 30 March 2023
(This article belongs to the Special Issue Advances in Gynecological Oncology: From Pathogenesis to Therapy)
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.
