Advances in the relationship of immune checkpoint inhibitors and DNA damage repair

Curr Res Transl Med. 2025 Jan 11;73(2):103494. doi: 10.1016/j.retram.2025.103494. Online ahead of print.

Abstract

Cancer immunotherapy, alongside surgery, radiation therapy, and chemotherapy, has emerged as a key treatment modality. Immune checkpoint inhibitors (ICIs) represent a promising immunotherapy that plays a critical role in the management of various solid tumors. However, the limited efficacy of ICI monotherapy and the development of primary or secondary resistance to combination therapy remain a challenge. Consequently, identifying molecular markers for predicting ICI efficacy has become an area of active clinical research. Notably, the correlation between DNA damage repair (DDR) mechanisms and the effectiveness of ICI treatment has been established. This review outlines the two primary pathways of DDR, namely, the homologous recombination repair pathway and the mismatch repair pathway. The relationship between these key genes and ICIs has been discussed and the potential of these genes as molecular markers for predicting ICI efficacy summarized.

Keywords: Biopredictive markers; DNA damage repair (DDR); Homologous recombination repair; Immune checkpoint inhibitors (ICIs); Mismatch repair.

Publication types

  • Review