GADD45: a crucial component of the DNA damage response and a potential cancer therapeutic target

The Growth Arrest and DNA Damage-Inducible 45 (GADD45) proteins, including GADD45α, GADD45β, and GADD45γ, play a crucial role in the cellular stress response and maintaining genome stability. These proteins are involved in various biological processes, including cell cycle arrest, DNA repair, apoptosis, and senescence, particularly when cells encounter genotoxic stress.

This review outlines the isoform-specific functions of GADD45 proteins in controlling DNA repair, apoptosis, and stress responses, emphasizing their context-dependent effects on cancer progression. We analyze emerging evidence highlighting their dual roles and discuss the potential of targeting GADD45 pathways in cancer therapy. This review was created through an extensive literature search and critical analysis of peer-reviewed articles obtained from PubMed, Scopus, Web of Science, and Google Scholar databases. The search covered literature published from 1994 to 2024, with a focus on recent studies (2018-2024) that examined molecular mechanisms, clinical correlations, and therapeutic implications of GADD45 signaling.

In summary, the GADD45 family serves as a crucial link between stress signaling, genomic stability, and immune regulation. Gaining a clearer understanding of their isoform-specific and context-dependent functions will be vital to fully leverage their potential as biomarkers and therapeutic targets in precision oncology.