Organoid of ovarian cancer: genomic analysis and drug screening

Organoid of ovarian cancer: genomic analysis and drug screening
Amir Ali Mousavi Salehi,^1,* Golshan Shahebrahimi,²
1. Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
2. Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Introduction: Cancer is one of the leading causes of deaths worldwide . Ovarian cancer (OC) has the highest mortality rate among gynecological tumors that threaten women’s health and life . Most cases (70%) are diagnosed at an advanced stage because the clinical manifestations of early OC are hidden or unspecific. Traditional and novel treatment schemes for this illness have progressed in the past decades, but the lack of early diagnosis and the poor efficiency of postoperative chemotherapy restrict the improvement in the 5-year survival rate of patients with OC . Therefore, research on OC focuses on determining highly specific and sensitive tumor markers for early diagnosis and prognosis evaluation (diagnostic aspect) and on exploring new strategies (therapeutic aspect), such as targeted therapy and immunotherapy. Preclinical models that can accurately recapitulate the biological characteristics of tumors in vivo are essential in this process. OC cell lines used to have a dominant role in OC biology, but have been gradually replaced by patient-derived xenograft (PDX). In the era of precision medicine, preclinical research platform derived from each individual has become indispensable, and high-throughput genomic analysis has been widely used to search for effective personalized treatment methods. Organoid is a powerful tool for precision medicine and drug screening . This technique can maintain the characteristics of tumor and its microenvironment in vivo to the greatest extent and can rectify the shortcomings of single cell lines in testing new drugs. The organoid maintains homology with primary tumors for a long time; hence, its drug sensitivity is better than that of cell lines during drug screening. Tumor-like organs are easy to replicate and pass on to form a biobank, which can be used for large-throughput gene analysis and drug screening. These organs can maintain the genetic heterogeneity of tumors and can mimic a hypoxic microenvironment. The organoid is a 3D tissue model directly induced by stem cells and a newly emerged preclinical model. Its application has been extended to many fields. At present, the organoid can be produced from primary prostate, colon, and pancreatic cancers . The OC organoid can multiply normal and precancerous cells, and its success rate is higher than those of PDX and spheroid. Organoids can be cultured from different tissues of different patients, such as primary and metastatic tumors, blood tissue, ascites, pleural effusion drainage, and normal FT and OSE.
Methods: This systematic study was mentioned using key words and referring to reliable scientific databases such as Scopus, PubMed, Google Scholar and ProQuest from the studies that were conducted until 2023 and a total of 15 articles were reviewed.
Results: The ovarian cancer organoid is a stable tumor model that can be used for gene analysis, predicting drug sensitivity, and searching for specific biomarkers. This cell culture model can be used for gene manipulation and drug screening. Organoid is a useful tool in the study of targeted gene therapy and provides a suitable environment for studying immunotherapy. The organoid can establish various OC subtypes, including precancerous cells and normal tissues and therefore can be used to study tumor evolution. Salama’s team used organoids to show the process of Helicobacter pylori colonization in gastric epithelium that may cause cell transformation . Scanu’s team used gallbladder organoids to assess the role of Salmonella in the development of gallbladder cancer and showed that this infection can activate Akt and MAPK signaling pathways. In the future, the organoid must be employed to study the evolution from normal tissues, precancerous lesions, low-grade malignancy, and finally to high-grade malignancy.The main gene changes are analyzed to achieve early detection, prevention, and treatment. The results will be of great importance for the early screening of OC.
Conclusion: As a new preclinical model, the organoid needs improvements, specifically its success rate. Its tumor microenvironment is single and lacks matrix, blood vessels, and immune cells. Further modifications can render the Ovarian Cancer organoid an efficient and robust method for the primary organ culture of gynecological tumors and a highly reliable research approach for targeted therapy and immunotherapy.
Keywords: Drug screening; Immunotherapy; Organoid; Ovarian cancer; Targeted therapy.