Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, 515041, China; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, 515041, China.
Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, 515041, China; Institute of Oncologic Pathology, Shantou University Medical College, Shantou, 515041, China.
Cancer Lett. 2020 Apr 10;475:65-78. doi: 10.1016/j.canlet.2020.01.018. Epub 2020 Jan 22.
Despite therapeutic advances, resistance to chemotherapy remains a major challenge to patients with malignancies. Rho GTPases are essential for the development and progression of various diseases including cancer, and a vast number of studies have linked Rho GTPases to chemoresistance. Therefore, understanding the underlying mechanisms can expound the effects of Rho GTPases towards chemotherapeutic agents, and targeting Rho GTPases is a promising strategy to downregulate the chemo-protective pathways and overcome chemoresistance. Importantly, exceptions in certain biological conditions and interactions among the members of Rho GTPases should be noted. In this review, we focus on the role of Rho GTPases, particularly Rac1, in regulating chemoresistance and provide an overview of their related mechanisms and available inhibitors, which may offer novel options for future targeted cancer therapy.
尽管治疗方法有所进步，但恶性肿瘤患者对化疗的耐药性仍然是一个主要挑战。Rho GTPases 对于各种疾病的发展和进展至关重要，包括癌症，大量研究将 Rho GTPases 与化疗耐药性联系起来。因此，了解潜在的机制可以阐明 Rho GTPases 对化疗药物的作用，靶向 Rho GTPases 是下调化疗保护途径和克服化疗耐药性的一种有前途的策略。重要的是，应该注意到某些生物学条件下的例外情况和 Rho GTPases 成员之间的相互作用。在这篇综述中，我们重点介绍 Rho GTPases（特别是 Rac1）在调节化疗耐药性中的作用，并概述其相关机制和可用抑制剂，这可能为未来的靶向癌症治疗提供新的选择。
