The Rho/ROCK pathway is involved in numerous pivotal cellular processes that have made it an area of intense study in cancer medicine, however, Rho-associated coiled-coil containing protein kinase (ROCK) inhibitors are yet to make an appearance in the clinical cancer setting. Their performance as an anti-cancer therapy has been varied in pre-clinical studies, however, they have been shown to be effective vasodilators in the treatment of hypertension and post-ischaemic stroke vasospasm. This review addresses the various roles the Rho/ROCK pathway plays in angiogenesis, tumour vascular tone and reciprocal feedback from the tumour microenvironment and explores the potential utility of ROCK inhibitors as effective vascular normalising agents. ROCK inhibitors may potentially enhance the delivery and efficacy of chemotherapy agents and improve the effectiveness of radiotherapy. As such, repurposing of these agents as adjuncts to standard treatments may significantly improve outcomes for patients with cancer. A deeper understanding of the controlled and dynamic regulation of the key components of the Rho pathway may lead to effective use of the Rho/ROCK inhibitors in the clinical management of cancer.

中文翻译：

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Rho 相关激酶信号传导和癌症微环境：新的生物学意义和治疗机会


Rho/ROCK 通路涉及许多关键的细胞过程，这使其成为癌症医学中重点研究的领域，然而，Rho 相关的卷曲螺旋蛋白激酶 (ROCK) 抑制剂尚未出现在临床癌症中环境。它们作为抗癌疗法的性能在临床前研究中各不相同，但是，它们已被证明是治疗高血压和缺血性中风后血管痉挛的有效血管扩张剂。本综述讨论了 Rho/ROCK 通路在血管生成、肿瘤血管张力和肿瘤微环境相互反馈中发挥的各种作用，并探讨了 ROCK 抑制剂作为有效血管正常化剂的潜在用途。 ROCK 抑制剂可能会增强化疗药物的输送和疗效，并提高放疗的有效性。因此，重新利用这些药物作为标准治疗的辅助手段可能会显着改善癌症患者的预后。更深入地了解 Rho 通路关键成分的受控和动态调节可能会导致 Rho/ROCK 抑制剂在癌症临床治疗中的有效使用。