Dutcher Janice P, Flippot Ronan, Fallah Jaleh, Escudier Bernard
Cancer Research Foundation of New York, Chappaqua, NY.
Deptartment of Cancer Medicine, Institute Gustave Roussy, Villejuif, France.
Am Soc Clin Oncol Educ Book. 2020 Mar;40:1-18. doi: 10.1200/EDBK_280817.
The treatment of advanced renal cell carcinoma (RCC) has evolved dramatically over the past 30 years, as has a better understanding of the biology of the disease, knowledge of multiple subtypes with distinct molecular abnormalities, and improved comprehension of the perturbed pathways that lead to the development and growth of RCC. This is no longer a monolithic disease, although the majority of tumors are of the clear cell subtype. However, progress is being made in other subtypes as well, as molecular profiles are better understood and as new agents show activity. Immunotherapies remain a major category of treatment, from cytokines to checkpoint inhibitors to ex vivo activated cellular therapy. Antiangiogenesis tyrosine kinase inhibitors are also an important part of the armamentarium. Because these approaches have evolved, we are now in the era of combination therapy using agents of differing mechanisms to try to achieve synergy to increase response rates and create durable responses leading to prolonged survival. Renal cell carcinoma as a tumor is unique in that there has always been a subset of patients who achieve complete responses that last for many years without subsequent treatment. Thus, the goal of further development is to enlarge this subset using new therapeutic approaches and to achieve further durable responses and treatment-free survival.
在过去30年里，晚期肾细胞癌（RCC）的治疗发生了巨大变化，对该疾病生物学的理解更加深入，对具有不同分子异常的多种亚型有了认识，对导致RCC发生和发展的紊乱通路也有了更好的理解。尽管大多数肿瘤是透明细胞亚型，但RCC已不再是单一的疾病。不过，随着分子特征被更好地了解以及新药物显示出活性，其他亚型的治疗也取得了进展。免疫疗法仍然是主要的治疗类别，从细胞因子到检查点抑制剂，再到体外激活的细胞疗法。抗血管生成酪氨酸激酶抑制剂也是治疗手段的重要组成部分。由于这些治疗方法不断发展，我们现在处于联合治疗时代，使用不同作用机制的药物试图实现协同作用，以提高缓解率并产生持久反应，从而延长生存期。肾细胞癌作为一种肿瘤的独特之处在于，总有一部分患者能够实现完全缓解，且无需后续治疗就能持续多年。因此，进一步发展的目标是通过新的治疗方法扩大这一群体，并实现更持久的反应和无治疗生存期。
