Kumar K S Praveen, Jyothi M N, Prashant Akila
Department of Medical Genetics, JSS Medical College and Hospital, JSS-AHER, 570015, Mysuru, India, Karnataka.
Department of Biochemistry, JSS Medical College and Hospital, JSS-AHER, Karnataka, 570015, Mysuru, India.
Mol Biol Rep. 2025 Apr 25;52(1):426. doi: 10.1007/s11033-025-10536-w.
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.
染色质结构域解旋酶DNA结合蛋白1（CHD1）是染色质动力学的核心调节因子，对基因表达、DNA修复和基因组稳定性有深远影响。本综述批判性地探讨了CHD1在癌症生物学中的作用，强调了其复杂的、依赖于背景的功能。在前列腺癌中，CHD1既作为肿瘤抑制因子，又作为神经内分泌分化的促进因子，其缺失与侵袭性表型、对雄激素受体疗法的耐药性以及与PTEN缺失的合成致死性有关。除前列腺癌外，CHD1还与乳腺癌、卵巢癌和血液系统癌症有关，在这些癌症中，它调节染色质可及性、转录调控和治疗耐药性。尽管CHD1有望成为生物标志物和治疗靶点，但由于其双重作用和癌症特异性效应，它也带来了挑战。该综述还强调了关键差距，包括需要对CHD1与免疫途径的相互作用、合成致死机制以及治疗耐药性中的染色质重塑进行高分辨率研究。利用CHD1的分子复杂性可能为癌症的创新诊断和治疗策略指明方向，但其在非前列腺癌中的作用仍未得到充分探索，值得进一步研究。
