Novel Therapies for Metastatic Renal Cell Carcinoma: Efforts to Expand beyond the VEGF/mTOR Signaling Paradigm
Open Access
- 1 March 2012
- journal article
- review article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Therapeutics
- Vol. 11 (3), 526-537
- https://doi.org/10.1158/1535-7163.mct-11-0806
Abstract
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. Mol Cancer Ther; 11(3); 526–37. ©2012 AACR.Keywords
This publication has 96 references indexed in Scilit:
- A phase II study evaluating the efficacy and safety of AMG 102 (rilotumumab) in patients with recurrent glioblastomaNeuro-Oncology, 2011
- A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancerBritish Journal of Cancer, 2010
- Improved Survival with Ipilimumab in Patients with Metastatic MelanomaThe New England Journal of Medicine, 2010
- Sipuleucel-T Immunotherapy for Castration-Resistant Prostate CancerThe New England Journal of Medicine, 2010
- The Efficacy of the Novel Dual PI3-Kinase/mTOR Inhibitor NVP-BEZ235 Compared with Rapamycin in Renal Cell CarcinomaClinical Cancer Research, 2010
- Kinase requirements in human cells: III. Altered kinase requirements inVHL−/− cancer cells detected in a pilot synthetic lethal screenProceedings of the National Academy of Sciences of the United States of America, 2008
- Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trialThe Lancet, 2008
- Ipilimumab (Anti-CTLA4 Antibody) Causes Regression of Metastatic Renal Cell Cancer Associated With Enteritis and HypophysitisJournal of Immunotherapy, 2007
- Sorafenib in Advanced Clear-Cell Renal-Cell CarcinomaThe New England Journal of Medicine, 2007
- Angiopoietin-1 Inhibits Endothelial Cell Apoptosis via the Akt/Survivin PathwayJournal of Biological Chemistry, 2000