The Therapeutic Landscape of Renal Cell Carcinoma: From the Dark Age to the Golden Age.
The Therapeutic Landscape of Renal Cell Carcinoma: From the Dark Age to the Golden Age.
复制标题
DOI：
10.1016/j.semnephrol.2019.12.004
复制
发表时间：
2020-01
影响因子：
3.3
通讯作者：
Hsieh JJ
中科院分区：
文献类型：
--
作者：
Huang JJ;Hsieh JJ
肾细胞癌（RCC）的肿瘤治疗在过去二十年中经历了一场革命，摆脱了2004年前的黑暗时代，IL-2和IFN-α是唯一的治疗选择，仅在5 - 10%的转移性患者中诱导治疗反应。2005年，抗VEGFR2的抗血管生成酪氨酸激酶抑制剂（TKI）和mTORC 1抑制剂的开发引入了现代，总体生存期和无进展生存期更好，更多患者（30 - 40%）对这些靶向治疗药物有反应并受益（约80%）。随着免疫检查点抑制剂（ICI）的使用，免疫肿瘤学（IO）时代的到来将我们带入了转移性RCC治疗的黄金时代，（抗PD-1/L1和抗CTLA-4）或一种TKI加一种ICI（抗PD-1/L1）已经重塑了透明细胞RCC（ccRCC）的治疗前景，透明细胞RCC是最常见的RCC亚型，反应率约为60%，疾病控制率约为90%，进一步提高了转移性RCC的生存率。基于对肾癌的生物学、病理学和基因组学以及相应治疗结果的研究，正在进行令人兴奋的临床试验，以利用互补/协同分子机制。这将使我们能够进入精准医学的钻石时代，可以根据个体肾脏肿瘤的特定生物学和病理学情况量身定制特定治疗，以提供更有效但毒性更小的治疗。
Oncologic treatments for renal cell carcinoma (RCC) have undergone a revolution in the past two decades, moving away from the pre-2004 Dark Age where IL-2 and IFN-α were the only therapeutic options and only induced treatment responses in 5–10% of metastatic patients. The development of anti-angiogenic tyrosine kinase inhibitors (TKIs) against VEGFR2 and inhibitors of mTORC1 introduced the Modern Age in 2005 with better overall and progression free survival and a greater number of patients (30–40%) responding to and (~80%) benefiting from these targeted therapeutic agents. The coming of age of the immuno-oncology (IO) era with the use of immune checkpoint inhibitors (ICIs) have ushered us into the Golden Age of metastatic RCC care, where combined administrations of two ICIs (anti-PD-1/L1 and anti-CTLA-4) or one TKI plus one ICI (anti-PD-1/L1) have recast the treatment landscape of clear cell RCC (ccRCC), the most common RCC subtype, with ~60% response rate and ~90% disease control rate that further improve metastatic RCC survival. Exciting clinical trials are in the pipeline exploiting complementary/synergistic molecular mechanisms, based on studies investigating the biology, pathology and genomics of renal carcinoma and the respective treatment outcome. This will enable us to enter the Diamond Age of precision medicine where a specific treatment can be tailored to the specific biological and pathological circumstance of an individual kidney tumor to offer more effective yet less toxic therapy.
登录
查看更多内容
DOI：
10.1056/nejmoa1510016
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Choueiri TK;Escudier B;Powles T;Mainwaring PN;Rini BI;Donskov F;Hammers H;Hutson TE;Lee JL;Peltola K;Roth BJ;Bjarnason GA;Géczi L;Keam B;Maroto P;Heng DY;Schmidinger M;Kantoff PW;Borgman-Hagey A;Hessel C;Scheffold C;Schwab GM;Tannir NM;Motzer RJ;METEOR Investigators
通讯作者：
METEOR Investigators
影响因子：
16.6
作者：
Chen F;Zhang Y;Bossé D;Lalani AA;Hakimi AA;Hsieh JJ;Choueiri TK;Gibbons DL;Ittmann M;Creighton CJ
通讯作者：
Creighton CJ
影响因子：
45.3
作者：
Escudier, Bernard;Eisen, Tim;Bukowski, Ronald M.
通讯作者：
Bukowski, Ronald M.
影响因子：
168.9
作者：
Escudier, Bernard;Pluzanska, Anna;Moore, Nicola
通讯作者：
Moore, Nicola
DOI：
10.1042/bss0700147
发表时间：
2003-01-01
期刊：
PROTEASES AND THE REGULATION OF BIOLOGICAL PROCESSES
影响因子：
--
作者：
Docherty, AJP;Crabbe, T;Groom, CR
通讯作者：
Groom, CR