Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. Electronic address: https://twitter.com/@yuangao_yg.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Curr Opin Genet Dev. 2024 Apr;85:102162. doi: 10.1016/j.gde.2024.102162. Epub 2024 Feb 24.
Aberrant chromatin regulation can promote the initiation and progression of human cancer. An improved understanding of such mechanisms has resulted in the identification of cancers with an enhanced dependency on specific chromatin regulatory proteins relative to nonmalignant cell types. Hence, targeting of such complexes with small molecules has significant therapeutic potential in oncology. In recent years, several drugs have been developed and evaluated in human cancer patients, which can influence tumor biology by reprogramming of chromatin structure. In this review, we summarize several of the known mechanisms that endow cancer cells with a powerful dependency on chromatin regulation that exceeds the requirements for normal tissue homeostasis. We also summarize the remarkable small-molecule inhibitors that exploit chromatin regulator dependencies with a clear therapeutic benefit in human cancer patients.
异常的染色质调控可以促进人类癌症的发生和发展。对这些机制的深入了解已经确定了一些癌症，相对于非恶性细胞类型，这些癌症对特定的染色质调控蛋白具有更高的依赖性。因此，用小分子靶向这些复合物在肿瘤学中有很大的治疗潜力。近年来，已经开发并评估了几种药物用于人类癌症患者，这些药物可以通过重编程染色质结构来影响肿瘤生物学。在这篇综述中，我们总结了几种已知的机制，这些机制赋予了癌细胞对染色质调控的强大依赖性，超过了正常组织内稳态的要求。我们还总结了利用染色质调节因子依赖性的显著小分子抑制剂，这些抑制剂在人类癌症患者中有明确的治疗益处。
