Patient-Derived Organoids: The Beginning of a New Era in Ovarian Cancer Disease Modeling and Drug Sensitivity Testing

Abstract

Ovarian cancer (OC) is the leading cause of death from gynecological malignancies. Despite great advances in treatment strategies, therapeutic resistance and the gap between preclinical data and actual clinical efficacy justify the necessity of developing novel models for investigating OC. Organoids represent revolutionary three-dimensional cell culture models, deriving from stem cells and reflecting the primary tissue’s biology and pathology. The aim of the current review is to study the current status of mouse- and patient-derived organoids, as well as their potential to model carcinogenesis and perform drug screenings for OC. Herein, we describe the role of organoids in the assessment of high-grade serous OC (HGSOC) cells-of-origin, illustrate their use as promising preclinical OC models and highlight the advantages of organoid technology in terms of disease modelling and drug sensitivity testing.

The Role of Patient-Derived Organoids in Triple-Negative Breast Cancer Drug Screening

“…Of note, these disadvantages are not limited to only TNBC patient-derived organoids. Similar limitations have been described for other cancer entities as well, thus outlining the imperative need for further research in the field of organoid culture optimization [ 22 , 23 ].…”

“…Since their initial application, patient-derived organoids have provided great insights into the pathophysiology of numerous cancer entities and, especially, shed light on obscure and otherwise unexplainable aspects related to the pathogenesis of scarce or complex tumors [ 20 , 21 , 22 , 23 ]. TNBC belongs to the multifaceted and, consequently, aggressive subtypes of breast cancer, as it does not abide by the well-understood hormonal pathways that characterize the more common hormone-receptor positive breast cancer entities but develops and spreads through diverse and extremely complicated molecular mechanisms [ 24 ].…”

The Emerging Role of Histone Deacetylase Inhibitors in Cervical Cancer Therapy

“…Only two research groups conducted clinical trials and published the most promising results concerning the application of valproic acid (in combination with other treatment agents) in cervical carcinoma patients. Consequently, future studies could incorporate further cervical cancer cell lines but should also take into consideration the advantages of the employment of more reliable, three-dimensional testing models including organoids, which have so far been described as the most useful drug sensitivity screening platforms in different types of (gynecological) cancer [ 139 , 140 , 141 ]. Preferably, the conduction of clinical trials with large patient collectives could help verify the clinical utility and safety of diverse HDACIs in cervical cancer therapy, as well as inspect eventual adverse side effects resulting from their application to women.…”

Three Dimensional Models of Endocrine Organs and Target Tissues Regulated by the Endocrine System

“…Work with organoids is progressing rapidly, where biobanks from primary tumors and their metastasis from multiple ovarian cancer subtypes have been established [ 163 , 173 , 174 , 175 ]. Whole-genome sequencing and histology assessments indicate that PDOs from ovarian cancers mirror the features of parental tumors in addition to sharing similarities in response to chemotherapy treatments [ 38 , 163 , 176 , 177 , 178 ].…”