Emerging Therapeutics to Overcome Chemoresistance in Epithelial Ovarian Cancer: A Mini-Review

Abstract

Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecologic malignancy. One of the leading causes of death in high-grade serous ovarian cancer (HGSOC) is chemoresistant disease, which may present as intrinsic or acquired resistance to therapies. Here we discuss some of the known molecular mechanisms of chemoresistance that have been exhaustively investigated in chemoresistant ovarian cancer, including drug efflux pump multidrug resistance protein 1 (MDR1), the epithelial–mesenchymal transition, DNA damage and repair capacity. We also discuss novel therapeutics that may address some of the challenges in bringing approaches that target chemoresistant processes from bench to bedside. Some of these new therapies include novel drug delivery systems, targets that may halt adaptive changes in the tumor, exploitation of tumor mutations that leave cancer cells vulnerable to irreversible damage, and novel drugs that target ribosomal biogenesis, a process that may be uniquely different in cancer versus non-cancerous cells. Each of these approaches, or a combination of them, may provide a greater number of positive outcomes for a broader population of HGSOC patients.

Sox2 promotes expression of the ST6Gal-I glycosyltransferase in ovarian cancer cells

“…Ovarian cancer is the deadliest gynecological malignancy due primarily to late detection and development of drug resistance [1,2]. While most ovarian cancer patients respond initially to treatment, acquired resistance is common, leading to tumor recurrence [2].…”

“…Ovarian cancer is the deadliest gynecological malignancy due primarily to late detection and development of drug resistance [1,2]. While most ovarian cancer patients respond initially to treatment, acquired resistance is common, leading to tumor recurrence [2]. Cancer stem cells (CSCs) are thought to be principal drivers of ovarian cancer progression and recurrence due to their high degree of resistance to both chemotherapy and microenvironmental stressors such as hypoxia [3,4].…”

Determination of chemoresistance of ovarian cancer cells in vitro

“…о гетерозиготности и клональной эволюции опухолей яичников хорошо согласуются с этими представлениями [12]. Тем не менее скорость приобретения химиорезистентности свидетельствует о существовании в опухолевых клетках механизмов адаптации к условиям существования в присутствии цитотоксических агентов [8], а также о возможности горизонтального переноса генетической информации между опухолевыми клетками [13,14].…”

Multi-Drug-Resistance in Drug-Naive and Drug-Exposed Ovarian Cancer Cell Lines Responds Differently to Cell Culture Dimensionality

“…However, effect of chemotherapeutic treatment is limited by chemoresistance. Approximately 30% of patients have preintrinsic chemoresistance and others eventually acquire chemoresistance during continuing exposure to chemotherapeutic agents (2). Because chemoresistance is among the main reasons preventing progress in OC treatment, there has been intensive research in this field.…”