Targeting the DNA repair pathway for breast cancer therapy: Beyond the molecular subtypes.

Biomed Pharmacother

Department of Breast Surgery, Guizhou Provincial People's Hospital, NO.83 Zhongshan East Road, Guiyang, Guizhou Province 550002, China. Electronic address:

Published: December 2023

AI Article Synopsis

  • DNA repair is essential for cell health, preventing DNA damage that can lead to cancer; dysfunctions in this process are linked to cancer development.
  • Advances in targeted therapy, particularly with PARP1 inhibitors, show promise for treating breast cancer in patients with BRCA1/2 mutations, highlighting the importance of the DNA repair signaling pathway.
  • The review outlines current research on BRCA-related treatments, evaluations of various DNA repair inhibitors, and their clinical implications for different breast cancer subtypes, while also forecasting future developments in cancer therapy.

Article Abstract

DNA repair is a vital mechanism in cells that protects against DNA damage caused by internal and external factors. It involves a network of signaling pathways that monitor and transmit damage signals, activating various cellular activities to repair DNA damage and maintain genomic integrity. Dysfunctions in this repair pathway are strongly associated with the development and progression of cancer. However, they also present an opportunity for targeted therapy in breast cancer. Extensive research has focused on developing inhibitors that play a crucial role in the signaling pathway of DNA repair, particularly due to the remarkable success of PARP1 inhibitors (PARPis) in treating breast cancer patients with BRCA1/2 mutations. In this review, we summarize the current research progress and clinical implementation of BRCA and BRCAness in targeted treatments for the DNA repair pathway. Additionally, we present advancements in diverse inhibitors of DNA repair, both as individual and combined approaches, for treating breast cancer. We also discuss the clinical application of DNA repair-targeted therapy for breast cancer, including the rationale, indications, and summarized clinical data for patients with different breast cancer subtypes. We assess their influence on cancer progression, survival rates, and major adverse reactions. Last, we anticipate forthcoming advancements in targeted therapy for cancer treatment and emphasize prospective areas of development.

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Source
http://dx.doi.org/10.1016/j.biopha.2023.115877DOI Listing

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