Predictors of Response to Targeted Therapy in Renal Cell Carcinoma

Abstract

Context.—The prognosis for patients with metastatic renal cell carcinoma is poor, with an average 5-year survival of approximately 10%. Use of traditional cytokine therapy, specifically high-dose interleukin 2, is limited by significant toxicity. Better understanding of the molecular pathogenesis of renal cell carcinoma has led to the development of targeted therapies to inhibit specific cellular pathways leading to tumorigenesis. These drugs provide improved survival with a more favorable toxicity profile. There is ongoing investigation of markers that predict response of an individual patient to different targeted therapies. Objective.—To explain the molecular basis for vascular endothelial growth factor inhibitor (antiangiogenic) and mammalian target of rapamycin inhibitor therapies for renal cell carcinoma, summarize the clinical trials demonstrating the effectiveness of these drugs, and describe the biomarkers shown to correlate with outcome in patients treated with targeted therapy. Data Sources.—All included sources are from peer-reviewed journals in PubMed (US National Library of Medicine). Conclusion.—Emerging evidence shows promise that biomarkers will be useful for predicting an individual patient's response to targeted therapy, leading to a more personalized approach to treating renal cell carcinoma.

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

“…Knockdown of Gal-1 in RCC Cells Reduced Cell Invasion, Clonogenic Ability, and EMT In Vitro and Tumor Growth In Vivo Because up to 75% of patients with sporadic clear cell RCC have aberrant von Hippel-Lindau (VHL) tumor suppressor gene, 3 two VHL-mutant kidney cancer cell lines (786-O and A-498) were used in the following experiments. To investigate the role of Gal-1 in RCC progression, the vesicular stomatitis virus-G pseudotyped lentivirus-short hairpin RNA (shRNA) system was used to silence Gal-1 in both cell lines.…”

“…2 The 5-year survival rate of metastatic RCC is only 10% because of resistance to chemotherapy and radiation therapy. 3 Although cytokine therapy with IFN-a and IL-2 is the gold standard treatment, its overall efficacy rate is limited by its significant toxicity. 4 Recently, several molecular targeting drugs, including sunitinib and temsirolimus, have been approved for advanced RCC.…”

Relationships between the Effect of Sunitinib and Immature Blood Vessels in Metastatic Renal Cell Cancer

“…Numerous studies on clinicopathological criteria, von Hippel-Lindau status, serum cytokines, and angiogenic factors in relation to the TKI response have been reported [26]. Solid tumors recruit blood vessels from the neighboring tissues by angiogenesis.…”

Metastasis to the parotid region as an initial presentation of renal cell carcinoma: A case report

“…Combinatorial therapy strategies have not yet been demonstrated to be beneficial, with a number of combinations exhibiting excessive toxicity with marginal or inferior efficacy compared with that observed with the sequential use of agents (19). Ongoing investigations concerning the biomarkers that predict severe adverse events and the response of an individual patient to different targeted therapies will lead to a more personalized approach to treating mRCC (20,21). Additionally, novel immunological therapies are currently being developed to treat mRCC, including those that block cytotoxic T-lymphocyte antigen 4 (CTLA4) (11).…”