With six agents approved for metastatic renal cell carcinoma (mRCC) within the past 5 years, there has undoubtedly been progress in treating this disease.
However, the goal of cure remains elusive, and the agents nearest approval (i.e., axitinib and tivozanib) abide by the same paradigm as existing drugs (i.e., inhibition of VEGF or mTOR signaling). The current review will focus on investigational agents that diverge from this paradigm. Specifically, novel immunotherapeutic strategies will be discussed, including vaccine therapy, cytotoxic T-lymphocyte antigen 4 (CTLA4) blockade, and programmed death-1 (PD-1) inhibition, as well as novel approaches to angiogenesis inhibition, such as abrogation of Ang/Tie-2 signaling. Pharmacologic strategies to block other potentially relevant signaling pathways, such as fibroblast growth factor receptor or MET inhibition, are also in various stages of development. Although VEGF and mTOR inhibition have dramatically improved outcomes for patients with mRCCs, a surge above the current plateau with these agents will likely require exploring new avenues.
Written by:
Pal SK, Williams S, Josephson DY, Carmichael C, Vogelzang NJ, Quinn DI. Are you the author?
Division of Genitourinary Oncology, Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USA.
Reference: Mol Cancer Ther. 2012 Mar;11(3):526-37.
doi: 10.1158/1535-7163.MCT-11-0806
PubMed Abstract
PMID: 22351744
UroToday.com Renal Cancer Section