CHD1 dysregulation in cancer: bridging chromatin instability, therapy resistance, and immune evasion

Chromodomain-Helicase-DNA-binding protein 1 (CHD1) is a central regulator of chromatin dynamics, profoundly influencing gene expression, DNA repair, and genomic stability. This review critically explores CHD1's role in cancer biology, emphasizing its complex, context-dependent functions. In prostate cancer, CHD1 acts as both a tumour suppressor and a facilitator of neuroendocrine differentiation, with its loss linked to aggressive phenotypes, resistance to androgen receptor therapies, and synthetic lethality with PTEN loss. Beyond prostate cancer, CHD1 is implicated in breast, ovarian, and hematological cancers, where it modulates chromatin accessibility, transcription regulation, and therapy resistance. Despite its promise as a biomarker and therapeutic target, CHD1 presents challenges due to its dual roles and cancer-specific effects. The review also highlights critical gaps, including the need for high-resolution studies on CHD1's interactions with immune pathways, synthetic lethality mechanisms, and chromatin remodelling in treatment resistance. Leveraging CHD1's molecular complexities could show the way for innovative diagnostic and therapeutic strategies in cancer, but its role in non-prostate cancers remains underexplored, warranting further investigation.