Kanesvaran Ravindran, Tan Min-Han
Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Republic of Singapore.
Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Republic of Singapore ; Institute of Bioengineering and Nanotechnology, Singapore 138669, Republic of Singapore.
J Carcinog. 2014 Feb 20;13:3. doi: 10.4103/1477-3163.127638. eCollection 2014.
Advances in rationally targeted therapeutics over the last decade have transformed the clinical care of advanced kidney cancer. While oncologists consolidate the gains of the wave of new agents, comprising a panoply of anti-vascular endothelial growth factor multi-targeted tyrosine kinase inhibitors and inhibitors of the mammalian target of rapamycin (mTOR), there is an increasing sense that a plateau has been reached in the short term. It is sobering that all currently approved targeted therapies have not yielded durable remissions and remain palliative in intent. In the context of recent insights in kidney cancer biology, we review promising ongoing and future approaches for kidney cancer therapeutics aimed toward forging new paths in the systemic management of renal cell carcinoma. Broadly, candidate agents for such innovative strategies include immune check-point inhibitors, anti-cancer stem cell agents, next-generation anti-vascular endothelial growth factor receptor and anti-mTOR agents as well as more investigational agents in the preclinical and early clinical development settings.
在过去十年中,合理靶向治疗的进展改变了晚期肾癌的临床治疗。肿瘤学家在巩固一系列新药物(包括多种抗血管内皮生长因子多靶点酪氨酸激酶抑制剂和雷帕霉素哺乳动物靶点(mTOR)抑制剂)所取得成果的同时,越来越感觉到短期内已达到一个平台期。令人警醒的是,所有目前获批的靶向治疗都未能产生持久缓解,且本质上仍为姑息性治疗。结合肾癌生物学的最新见解,我们回顾了肾癌治疗中正在进行的和未来有前景的方法,旨在为肾细胞癌的全身管理开辟新途径。总体而言,此类创新策略的候选药物包括免疫检查点抑制剂、抗癌干细胞药物、下一代抗血管内皮生长因子受体和抗mTOR药物,以及处于临床前和早期临床开发阶段的更多研究性药物。