Sepe Pierangela, Ottini Arianna, Pircher Chiara Carlotta, Franza Andrea, Claps Melanie, Guadalupi Valentina, Verzoni Elena, Procopio Giuseppe
Department of Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy.
Cancers (Basel). 2021 Jul 28;13(15):3807. doi: 10.3390/cancers13153807.
Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non clear-cell RCC with untailored therapies. Due to their rarity, non-clear RCC are in fact under-represented in prospective randomized trials. Thus, treatment choices are based on extrapolating results from clear cell RCC trials, retrospective data, or case reports. Over the last two decades, various options have been considered as the mainstay for the treatment of metastatic RCC (mRCC), including angiogenesis inhibitors, vascular endothelial growth factor receptor inhibitors, other tyrosine kinase inhibitors (TKIs), as well as MET inhibitors and mammalian targeting of rapamycin (mTOR) inhibitors. More recently, the therapeutic armamentarium has been enriched with immunotherapy, alone or in combination with targeted agents that have been shown to significantly improve outcomes of mRCC patients, if compared to TKI single-agent. It has been widely proven that non-clear cell RCC is a morphologically and clinically distinct entity from its clear cell counterpart but more knowledge about its biology is certainly needed. Histology-specific collaborative trials are in fact now emerging to investigate different treatments for non-clear cell RCC. This review summarizes pathogenetic mechanisms of non-clear cell RCC, the evolution of treatment paradigms over the last few decades, with a focus on immunotherapy-based trials, and future potential treatment options.
非透明细胞肾细胞癌（RCC）包含几种罕见且描述甚少的疾病，其特征通常是预后不良且没有可用的标准治疗方法。它们临床管理方面的差距与在处理非透明细胞RCC治疗时缺乏针对性治疗的分子特征描述不佳有关。由于其罕见性，非透明RCC在前瞻性随机试验中的代表性不足。因此，治疗选择是基于从透明细胞RCC试验、回顾性数据或病例报告中推断结果。在过去二十年中，各种选择被视为转移性RCC（mRCC）治疗的主要手段，包括血管生成抑制剂、血管内皮生长因子受体抑制剂、其他酪氨酸激酶抑制剂（TKIs），以及MET抑制剂和哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂。最近，治疗手段已因免疫疗法而更加丰富，免疫疗法单独使用或与靶向药物联合使用，与TKI单药治疗相比，已显示可显著改善mRCC患者的预后。已广泛证明，非透明细胞RCC在形态学和临床上与其透明细胞对应物是不同的实体，但肯定需要更多关于其生物学的知识。事实上，目前正在出现针对特定组织学的协作试验，以研究非透明细胞RCC的不同治疗方法。本综述总结了非透明细胞RCC的发病机制、过去几十年治疗模式的演变，重点是基于免疫疗法的试验，以及未来潜在的治疗选择。
