Significance of tumor microenvironment in acquiring resistance to vascular endothelial growth factor‐tyrosine kinase inhibitor and recent advance of systemic treatment of clear cell renal cell carcinoma
Significance of tumor microenvironment in acquiring resistance to vascular endothelial growth factor‐tyrosine kinase inhibitor and recent advance of systemic treatment of clear cell renal cell carcinoma
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肿瘤微环境在血管内皮生长因子酪氨酸激酶抑制剂耐药中的意义及透明细胞肾细胞癌全身治疗的最新进展
DOI：
10.1111/pin.12984
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发表时间：
2020
影响因子：
2.2
通讯作者：
Oya Mototsugu
中科院分区：
文献类型：
--
作者：
Mikami Shuji;Mizuno Ryuichi;Kosaka Takeo;Tanaka Nobuyuki;Kuroda Naoto;Nagashima Yoji;Okada Yasunori;Oya Mototsugu
包括血管内皮生长因子-酪氨酸激酶抑制剂（VEGF - TKI）和哺乳动物雷帕霉素靶点（mTOR）抑制剂在内的全身疗法的发展，代表了肾细胞癌（RCC）患者治疗的重大突破。然而，在一些患者中观察到固有耐药，许多患者通常在开始全身治疗的几个月内出现获得性耐药。由于这些治疗方法很少能治愈患者，它们的目的是抑制肿瘤进展并延长生存期。因此，建立可靠的标准来预测对全身治疗的反应和耐药具有重要的临床意义，并且还需要阐明潜在的分子机制，以便未来开发更有效的治疗方法。本文综述了近年来肿瘤耐药分子机制的研究进展，重点关注RCC的形态特征、肿瘤血管生成、肿瘤免疫微环境及其与VEGF - TKI治疗的关系。最近使用免疫检查点抑制剂（ICI）和新开发的VEGF - TKI治疗晚期RCC似乎也有效，在一些RCC患者中观察到对ICI的稳定和持久的反应。本文简要介绍了这些新药及其疗效。
The development of systemic therapies, including vascular endothelial growth factor‐tyrosine kinase inhibitors (VEGF‐TKI) and mammalian target of rapamycin (mTOR) inhibitors, represents a major breakthrough in the treatment of patients with renal cell carcinoma (RCC). However, inherent resistance is observed in some patients and acquired resistance commonly develops in many patients within several months of the initiation of systemic therapies. Since these treatments rarely cure patients, their aim is to suppress tumor progression and prolong survival. Therefore, the establishment of dependable criteria that predict responses and resistance to systemic therapies is clinically important, and the underlying molecular mechanisms also need to be elucidated for the future development of more effective therapies. We herein review recent advances in research on the molecular mechanisms underlying resistance, with a focus on morphological characteristics, tumor angiogenesis, and the tumor immune microenvironment in RCC and their relationships with VEGF‐TKI treatments. Recent therapies using immune checkpoint inhibitors (ICI) and newly developed VEGF‐TKI also appear to be effective for advanced RCC, with stable and durable responses to ICI being observed in some RCC patients. These new drugs and their outcomes have been briefly described.