For more than three decades, platinum compounds have been the first line treatment for a wide spectrum of solid tumors. Yet, cisplatin resistance is a major impediment in cancer therapy, and deciphering the mechanisms underlying chemoresistance is crucial for the development of novel therapies with enhanced efficacy. The Rho subfamily of small GTPases plays a significant role in cancer progression, and a growing body of evidence points toward the involvement of these proteins in anticancer drug resistance, including cisplatin resistance. The cycling between active and inactive states, governed by the balance between their GEFs, GAPs and GDIs, RhoGTPases, acts as molecular switches with a pivotal role in actin cytoskeleton organization. The Rho subfamily of proteins is involved in many key cellular processes including adhesion, vesicular trafficking, proliferation, survival, cell morphology and cell-matrix interactions. Although RhoA, RhoB and RhoC are highly homologous and share some upstream regulators and downstream effectors, they each have different roles in cancer progression and chemoresistance. While RhoA and RhoC are upregulated in many tumors and can stimulate transformation, RhoB appears to exhibit tumor suppressor characteristics with proapoptotic effects. In the current review, we discuss the role of Rho subfamily of proteins in cancer, and focus on their involvement in intrinsic and acquired drug resistance.

中文翻译：

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RhoGTPases-细胞骨架组织与顺铂耐药性之间的新颖联系。

在过去的三十多年中，铂化合物一直是治疗各种实体瘤的一线治疗方法。然而，顺铂耐药性是癌症治疗中的主要障碍，而解密化学抗性的机制对于开发具有增强功效的新疗法至关重要。小GTP酶的Rho亚家族在癌症进展中起着重要作用，越来越多的证据表明这些蛋白质参与了包括顺铂耐药性在内的抗癌药物耐药性。活性和非活性状态之间的循环受其GEF，GAP和GDI，RhoGTPase之间的平衡支配，在肌动蛋白细胞骨架组织中起着至关重要的作用的分子开关。蛋白质的Rho亚家族参与许多关键的细胞过程，包括黏附，囊泡运输，增殖，存活，细胞形态和细胞基质相互作用。尽管RhoA，RhoB和RhoC高度同源并共享一些上游调节子和下游效应子，但它们各自在癌症进展和化学抗性中具有不同的作用。尽管RhoA和RhoC在许多肿瘤中上调并可以刺激转化，但RhoB似乎表现出具有抑癌作用的抑癌特性。在当前的审查中，我们讨论蛋白质的Rho亚家族在癌症中的作用，并着重于它们参与内在和获得性耐药的过程。它们各自在癌症进展和化学抗性中具有不同的作用。尽管RhoA和RhoC在许多肿瘤中上调并可以刺激转化，但RhoB似乎表现出具有抑癌作用的抑癌特性。在当前的审查中，我们讨论蛋白质的Rho亚家族在癌症中的作用，并着重于它们参与内在和获得性耐药的过程。它们各自在癌症进展和化学抗性中具有不同的作用。尽管RhoA和RhoC在许多肿瘤中上调并可以刺激转化，但RhoB似乎表现出具有抑癌作用的抑癌特性。在当前的审查中，我们讨论蛋白质的Rho亚家族在癌症中的作用，并着重于它们参与内在和获得性耐药的过程。