肾癌是一种高度异质性的恶性肿瘤,其特征是全球发病率和死亡率上升。多种信号通路的复杂相互作用和失调,包括vonHippel-Lindau(VHL)/缺氧诱导因子(HIF),磷酸肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR),河马-Yes相关蛋白(YAP),Wnt/β-catenin,环磷酸腺苷(cAMP),和肝细胞生长因子(HGF)/c-Met,有助于肾癌的发生和发展。虽然手术切除是局部肾癌的标准治疗方法,复发和转移继续带来重大挑战。晚期肾癌与不良预后相关,和目前的治疗方法,例如靶向药物和免疫疗法,有局限性。这篇综述全面概述了肾癌异常信号通路的分子机制。强调它们复杂的串扰和协同作用。我们讨论靶向治疗的最新进展,包括酪氨酸激酶抑制剂,和免疫疗法,如检查点抑制剂。此外,我们强调了多组学方法和网络分析在阐明控制肾癌发病机制的复杂调控网络方面的重要性.通过整合尖端研究和临床见解,这篇综述有助于创新诊断和治疗策略的发展,有可能改善风险分层,精准医学,最终,肾癌患者的预后。
Renal cancer is a highlyheterogeneous malignancy characterized by rising global incidence and mortalityrates. The complex interplay and dysregulation of multiple signaling pathways,including von Hippel-Lindau (VHL)/hypoxia-inducible factor (HIF), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), Hippo-yes-associated protein (YAP), Wnt/ß-catenin, cyclic adenosine monophosphate (cAMP), and hepatocyte growth factor (HGF)/c-Met, contribute to theinitiation and progression of renal cancer. Although surgical resection is thestandard treatment for localized renal cancer, recurrence and metastasiscontinue to pose significant challenges. Advanced renal cancer is associatedwith a poor prognosis, and current therapies, such as targeted agents andimmunotherapies, have limitations. This review presents a comprehensiveoverview of the molecular mechanisms underlying aberrant signaling pathways inrenal cancer, emphasizing their intricate crosstalk and synergisticinteractions. We discuss recent advancements in targeted therapies, includingtyrosine kinase inhibitors, and immunotherapies, such as checkpoint inhibitors.Moreover, we underscore the importance of multiomics approaches and networkanalysis in elucidating the complex regulatory networks governing renal cancerpathogenesis. By integrating cutting-edge research and clinical insights, this review contributesto the development of innovative diagnostic and therapeutic strategies, whichhave the potential to improve risk stratification, precision medicine, andultimately, patient outcomes in renal cancer.