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Unleashing the Power of Synthetic Lethality: Augmenting Treatment Efficacy through Synergistic Integration with Chemotherapy Drugs

Yajing Du, Lulu Luo, Xinru Xu, Xinbing Yang, Xueni Yang, Shizheng Xiong, Jiafeng Yu, Tingming Liang, Li Guo

2023Pharmaceutics12 citationsDOIOpen Access PDF

Abstract

Cancer is the second leading cause of death in the world, and chemotherapy is one of the main methods of cancer treatment. However, the resistance of cancer cells to chemotherapeutic drugs has always been the main reason affecting the therapeutic effect. Synthetic lethality has emerged as a promising approach to augment the sensitivity of cancer cells to chemotherapy agents. Synthetic lethality (SL) refers to the specific cell death resulting from the simultaneous mutation of two non-lethal genes, which individually allow cell survival. This comprehensive review explores the classification of SL, screening methods, and research advancements in SL inhibitors, including Poly (ADP-ribose) polymerase (PARP) inhibitors, Ataxia telangiectasia and Rad3-related (ATR) inhibitors, WEE1 G2 checkpoint kinase (WEE1) inhibitors, and protein arginine methyltransferase 5 (PRMT5) inhibitors. Emphasizing their combined use with chemotherapy drugs, we aim to unveil more effective treatment strategies for cancer patients.

Topics & Concepts

Synthetic lethalityChemotherapyWee1Poly ADP ribose polymeraseCancerMedicineCancer researchCancer cellPharmacologyPolymeraseDNA repairBiologyCell cycleEnzymeGeneInternal medicineBiochemistryCyclin-dependent kinase 1Cancer-related gene regulationCRISPR and Genetic EngineeringCAR-T cell therapy research