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Review
. 2022 Dec 18;14(24):6246.
doi: 10.3390/cancers14246246.

Mechanisms of Drug Resistance in Ovarian Cancer and Associated Gene Targets

Kharimat Lora Alatise  1 , Samantha Gardner  1 , Angela Alexander-Bryant  1
Affiliations
Review

Mechanisms of Drug Resistance in Ovarian Cancer and Associated Gene Targets

Kharimat Lora Alatise et al. Cancers (Basel). .

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.

Keywords: RNAi therapeutics; chemoresistance; drug resistance; gene targets; ovarian cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Generic scheme of drug efflux proteins. The adenosine triphosphate (ATP) Binding Cassette (ABC) family of membrane proteins enables the efflux of therapeutics. ABC transporters (light purple) use ATP to pump chemotherapeutics (dark purple) out of the cell.
Figure 2
Figure 2
The intrinsic and extrinsic apoptosis pathways. The extrinsic apoptosis pathway is initiated through ligand–receptor interactions. The intrinsic pathway is mediated by the release of Smac and cytochrome C from mitochondria (green). Inhibitory proteins (dark purple) can interrupt the caspase cascade (pink), ultimately preventing apoptosis.
Figure 3
Figure 3
(A) Increased expression of DNA damage and repair proteins can cause resistance to platinum-based chemotherapeutics in ovarian cancer. (B) DNA damage by chemotherapeutics results in the activation of four DNA repair pathways. Increased expression of proteins within these pathways (green) can reverse this damage through repair mechanisms.
Figure 4
Figure 4
Scheme of cancer stem cells (CSCs) depicting the role of CSCs in ovarian cancer recurrence. CSCs are inherently resistant to chemotherapy and radiation and remain in the tumor tissue after treatment, causing tumor cell production and tumor recurrence. Tumor cells (red), CSCs (yellow).
See this image and copyright information in PMC

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