Mechanisms of Drug Resistance in Ovarian Cancer and Associated Gene Targets

Abstract

In the United States, over 100,000 women are diagnosed with a gynecologic malignancy every year, with ovarian cancer being the most lethal. One of the hallmark characteristics of ovarian cancer is the development of resistance to chemotherapeutics. While the exact mechanisms of chemoresistance are poorly understood, it is known that changes at the cellular and molecular level make chemoresistance challenging to treat. Improved therapeutic options are needed to target these changes at the molecular level. Using a precision medicine approach, such as gene therapy, genes can be specifically exploited to resensitize tumors to therapeutics. This review highlights traditional and novel gene targets that can be used to develop new and improved targeted therapies, from drug efflux proteins to ovarian cancer stem cells. The review also addresses the clinical relevance and landscape of the discussed gene targets.

Long noncoding RNAs and mRNAs profiling in ovary during laying and broodiness in Taihe Black-Bone Silky Fowls (Gallus gallus Domesticus Brisson)

“…This kinase is crucial in responding to dehydration, salt load, and other forms of environmental stress [ 25 ]. Although the specific role of SGK1-OT1 in ovarian development remains unclear, the related gene SGK1 has been implicated in the progression of ovarian cancer and the development of resistance to treatment [ 26 , 27 ]. Overexpression of SGK1 promotes tumor cell proliferation and migration while inhibiting induced apoptosis in cancer, suggesting a potential role for SGK1, and by extension SGK1-OT1, in promoting cell survival and proliferation—traits characteristic of cancer cells.…”

Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients

“…Genomic instability, defined as an increased susceptibility of a cell's genome to acquire mutations, stems from defects in DNA repair mechanisms, replication errors, exposure to mutagenic agents, or other genetic or environmental factors, leading to high mutation rate and resulting in a heterogeneous tumor population with diverse genetic compositions [ 48 , 49 ].…”

“…Finally, HR and Non-Homologous End Joining (NHEJ) are two critical pathways for repairing DSBs. HR is an error-free repair process utilizing a sister chromatid as a template for repair, while NHEJ is an error-prone process directly joining broken end [ 49 ]. These cancers often exhibit inherent defects in DNA repair pathways, particularly in HR [ 68 ].…”

“…To explore potential novel therapeutic strategies to overcome resistance, researchers have developed several cellular models with acquired resistance. By continuous exposure of cancer cell lines to the drug, researchers can observe the emergence of resistance and possibly identify the molecular changes that occur [ 49 , 171 , 172 ]. Consequently, several studies have focused on understanding the effects of chemotherapy alone or in combination with other treatments to elucidate the underlying mechanisms [ 74 ].…”

Deciphering resistance mechanisms and novel strategies to overcome drug resistance in ovarian cancer: a comprehensive review

“…Genes associated with DR affect cellular processes, such as drug efflux, apoptosis, and DNA damage and repair. Additionally, cancer stem cells (CSCs) within ovarian tumor tissue contribute to chemoresistance [ 10 ].…”