Predictors of response to targeted therapy in renal cell carcinoma.
BACKGROUND
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.


METHODS
All included sources are from peer-reviewed journals in PubMed (US National Library of Medicine).


CONCLUSIONS
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.
Department of Pathology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, 251 E Huron St, Chicago, IL 60611, USA.
Laurie J
LJ
Eisengart
Gary R
GR
MacVicar
Ximing J
XJ
Yang
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics*; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics*; D058990:Molecular Targeted Therapy; D058570:TOR Serine-Threonine Kinases / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases