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.

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人类癌症患者靶向选择染色质复合物的治疗指数

异常的染色质调节可以促进人类癌症的发生和进展。对此类机制的进一步了解导致了相对于非恶性细胞类型对特定染色质调节蛋白依赖性增强的癌症的鉴定。因此，用小分子靶向此类复合物在肿瘤学中具有显着的治疗潜力。近年来，已经开发出多种药物并在人类癌症患者中进行了评估，这些药物可以通过染色质结构的重编程来影响肿瘤生物学。在这篇综述中，我们总结了几种已知的机制，这些机制赋予癌细胞对染色质调节的强烈依赖性，超出了正常组织稳态的要求。我们还总结了利用染色质调节依赖性的显着小分子抑制剂，对人类癌症患者具有明显的治疗益处。