Targeted therapy for renal cell carcinoma: a new treatment paradigm - PubMed (original) (raw)
Targeted therapy for renal cell carcinoma: a new treatment paradigm
Thomas E Hutson. Proc (Bayl Univ Med Cent). 2007 Jul.
Abstract
Metastatic clear cell renal cell cancer has traditionally been treated with cytokines (interferon or interleukin-2). Improved understanding of biology has engendered novel targeted therapeutic agents that have altered the natural history of this disease. The vascular endothelial growth factor and its related receptor and the mTOR signal transduction pathway have particularly been exploited. Sunitinib malate, sorafenib tosylate, temsirolimus, and bevacizumab have improved clinical outcomes in randomized trials. Other multitargeted tyrosine kinase inhibitors (lapatinib, axitinib, pazopanib) and antiangiogenic agents (VEGF Trap, lenalidomide) have also demonstrated activity in early studies. Combinations of these agents are being evaluated. The future of the therapy of renal cancer appears promising owing to the efficacy of these novel agents.
Figures
Figure
Consequences of mutation or inactivation of the von Hippel Lindau (VHL) gene. VHL normally encodes a protein (p-VHL) that targets hypoxia-inducible factor (HIF) for proteolysis. As a result of VHL inactivation, a defective p-VHL is produced and HIF is up-regulated, translocates to the nucleus, and results in the transcription of several genes involved in angiogenesis and tumor growth. These genes include vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor (TGF)-α, basic fibroblast growth factor (bFGF), carbonic anhydrase IX (CA IX) or G250, erythropoietin (EPO), and others. OH indicates hydroxyl group; Ub, ubiquitin; Glut-1, glucose transporter 1; PAI-1, plasminogen activator inhibitor 1. Adapted from Kim WY. J Clin Oncol 2004;22:4991–5004.
Similar articles
- Recent advances in the therapy of renal cancer.
Sonpavde G, Hutson TE. Sonpavde G, et al. Expert Opin Biol Ther. 2007 Feb;7(2):233-42. doi: 10.1517/14712598.7.2.233. Expert Opin Biol Ther. 2007. PMID: 17250461 Review. - Renal cell cancer.
Hutson TE, Figlin RA. Hutson TE, et al. Cancer J. 2007 Sep-Oct;13(5):282-6. doi: 10.1097/PPO.0b013e318156fe69. Cancer J. 2007. PMID: 17921725 Review. - Evolving role of novel targeted agents in renal cell carcinoma.
Hutson TE, Figlin RA. Hutson TE, et al. Oncology (Williston Park). 2007 Sep;21(10):1175-80; discussion 1184, 1187, 1190. Oncology (Williston Park). 2007. PMID: 17926797 Review. - Targeted therapy for advanced renal cell cancer (RCC): a Cochrane systematic review of published randomised trials.
Coppin C, Kollmannsberger C, Le L, Porzsolt F, Wilt TJ. Coppin C, et al. BJU Int. 2011 Nov;108(10):1556-63. doi: 10.1111/j.1464-410X.2011.10629.x. Epub 2011 Sep 27. BJU Int. 2011. PMID: 21952069 Review. - Targeting growth factor and antiangiogenic pathways in clear-cell renal cell carcinoma: rationale and ongoing trials.
Hutson TE, Sonpavde G, Galsky MD. Hutson TE, et al. Clin Genitourin Cancer. 2006 Dec;5 Suppl 1:S31-9. doi: 10.3816/cgc.2006.s.005. Clin Genitourin Cancer. 2006. PMID: 17239282 Review.
Cited by
- Improved identification of von Hippel-Lindau gene alterations in clear cell renal tumors.
Nickerson ML, Jaeger E, Shi Y, Durocher JA, Mahurkar S, Zaridze D, Matveev V, Janout V, Kollarova H, Bencko V, Navratilova M, Szeszenia-Dabrowska N, Mates D, Mukeria A, Holcatova I, Schmidt LS, Toro JR, Karami S, Hung R, Gerard GF, Linehan WM, Merino M, Zbar B, Boffetta P, Brennan P, Rothman N, Chow WH, Waldman FM, Moore LE. Nickerson ML, et al. Clin Cancer Res. 2008 Aug 1;14(15):4726-34. doi: 10.1158/1078-0432.CCR-07-4921. Clin Cancer Res. 2008. PMID: 18676741 Free PMC article. - Biomarkers of Renal Tumors: the Current State and Clinical Perspectives.
Golovastova MO, Korolev DO, Tsoy LV, Varshavsky VA, Xu WH, Vinarov AZ, Zernii EY, Philippov PP, Zamyatnin AA Jr. Golovastova MO, et al. Curr Urol Rep. 2017 Jan;18(1):3. doi: 10.1007/s11934-017-0655-1. Curr Urol Rep. 2017. PMID: 28110463 Review. - Obesity is associated with a higher risk of clear-cell renal cell carcinoma than with other histologies.
Lowrance WT, Thompson RH, Yee DS, Kaag M, Donat SM, Russo P. Lowrance WT, et al. BJU Int. 2010 Jan;105(1):16-20. doi: 10.1111/j.1464-410X.2009.08706.x. Epub 2009 Jul 6. BJU Int. 2010. PMID: 19583732 Free PMC article. - Methylnaltrexone potentiates the anti-angiogenic effects of mTOR inhibitors.
Singleton PA, Mambetsariev N, Lennon FE, Mathew B, Siegler JH, Moreno-Vinasco L, Salgia R, Moss J, Garcia JG. Singleton PA, et al. J Angiogenes Res. 2010 Feb 19;2(1):5. doi: 10.1186/2040-2384-2-5. J Angiogenes Res. 2010. PMID: 20298531 Free PMC article. - An Overview of Systemic Targeted Therapy in Renal Cell Carcinoma, with a Focus on Metastatic Renal Cell Carcinoma and Brain Metastases.
Semenescu LE, Kamel A, Ciubotaru V, Baez-Rodriguez SM, Furtos M, Costachi A, Dricu A, Tătăranu LG. Semenescu LE, et al. Curr Issues Mol Biol. 2023 Sep 21;45(9):7680-7704. doi: 10.3390/cimb45090485. Curr Issues Mol Biol. 2023. PMID: 37754269 Free PMC article. Review.
References
- Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics, 2006. CA Cancer J Clin. 2006;56(2):106–130. - PubMed
- Yagoda A, Abi-Rached B, Petrylak D. Chemotherapy for advanced renal-cell carcinoma: 1983–1993. Semin Oncol. 1995;22(1):42–60. - PubMed
- Motzer RJ, Vogelzang NJ. Chemotherapy for renal cell carcinoma. In: Raghaven D, Scher HI, Leibel SA, Lang P, editors. Principles and Practice of Genitourinary Oncology. Philadelphia: Lippincott-Raven; 1997. pp. 885–896.
- McDermott DF, Atkins MB. Application of IL-2 and other cytokines in renal cancer. Expert Opin Biol Ther. 2004;4(4):455–468. - PubMed
- Hutson TE, Quinn DI. Cytokine therapy: a standard of care for metastatic renal cell carcinoma? Clin Genitourin Cancer. 2005;4(3):181–186. - PubMed
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous