Astore Serena, Baciarello Giulia, Cerbone Linda, Calabrò Fabio
Medical Oncology, San Camillo Forlanini Hospital, Rome 00152, Italy.
Medical Oncology, IRCSS, National Cancer Institute Regina Elena, Rome 00128, Italy.
Cancer Drug Resist. 2023 Aug 2;6(3):517-546. doi: 10.20517/cdr.2023.33. eCollection 2023.
The introduction of first-line combinations had improved the outcomes for metastatic renal cell carcinoma (mRCC) compared to sunitinib. However, some patients either have inherent resistance or develop resistance as a result of the treatment. Depending on the kind of therapy employed, many factors underlie resistance to systemic therapy. Angiogenesis and the tumor immune microenvironment (TIME), nevertheless, are inextricably linked. Although angiogenesis and the manipulation of the tumor microenvironment are linked to hypoxia, which emerges as a hallmark of renal cell carcinoma (RCC) pathogenesis, it is only one of the potential elements involved in the distinctive intra- and inter-tumor heterogeneity of RCC that is still dynamic. We may be able to more correctly predict therapy response and comprehend the mechanisms underlying primary or acquired resistance by integrating tumor genetic and immunological markers. In order to provide tools for patient selection and to generate hypotheses for the development of new strategies to overcome resistance, we reviewed the most recent research on the mechanisms of primary and acquired resistance to immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) that target the vascular endothelial growth factor receptor (VEGFR).We can choose patients' treatments and cancer preventive strategies using an evolutionary approach thanks to the few evolutionary trajectories that characterize ccRCC.
与舒尼替尼相比，一线联合治疗的引入改善了转移性肾细胞癌（mRCC）的治疗效果。然而，一些患者要么存在内在抗性，要么在治疗过程中产生抗性。根据所采用的治疗类型，对全身治疗产生抗性的因素有很多。然而，血管生成与肿瘤免疫微环境（TIME）紧密相连。尽管血管生成和肿瘤微环境的调控与缺氧有关，缺氧是肾细胞癌（RCC）发病机制的一个标志，但它只是RCC独特的肿瘤内和肿瘤间异质性中仍在动态变化的潜在因素之一。通过整合肿瘤遗传和免疫标记物，我们或许能够更准确地预测治疗反应，并理解原发性或获得性抗性的潜在机制。为了提供患者选择工具，并为开发克服抗性的新策略提出假设，我们回顾了关于对免疫检查点抑制剂（ICI）和靶向血管内皮生长因子受体（VEGFR）的酪氨酸激酶抑制剂（TKI）原发性和获得性抗性机制的最新研究。由于ccRCC具有少数几种进化轨迹，我们可以采用进化方法来选择患者的治疗方案和癌症预防策略。
