Exploiting DNA Replication Stress as a Therapeutic Strategy for Breast Cancer

Authors

Jing Zhang
Doug W Chan
Shiaw-Yih Lin

Publication Date

11-1-2022

Journal

Biomedicines

Abstract

Proliferating cells rely on DNA replication to ensure accurate genome duplication. Cancer cells, including breast cancer cells, exhibit elevated replication stress (RS) due to the uncontrolled oncogenic activation, loss of key tumor suppressors, and defects in the DNA repair machinery. This intrinsic vulnerability provides a great opportunity for therapeutic exploitation. An increasing number of drug candidates targeting RS in breast cancer are demonstrating promising efficacy in preclinical and early clinical trials. However, unresolved challenges lie in balancing the toxicity of these drugs while maintaining clinical efficacy. Furthermore, biomarkers of RS are urgently required to guide patient selection. In this review, we introduce the concept of targeting RS, detail the current therapies that target RS, and highlight the integration of RS with immunotherapies for breast cancer treatment. Additionally, we discuss the potential biomarkers to optimizing the efficacy of these therapies. Together, the continuous advances in our knowledge of targeting RS would benefit more patients with breast cancer.

Keywords

breast cancer, replication stress, replication stress response, DNA replication, chemotherapy

Comments

Data Availability Statement

PMID: 36359297

DOI

10.3390/biomedicines10112775

PMID

36359297

PMCID

PMC9687274

PubMedCentral® Posted Date

November 2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes