mTOR pathway in renal cell carcinoma.
After decades of therapeutic nihilism in the treatment of advanced renal cell carcinoma, remarkable therapeutic strides have been made over the last few years. Early forays into molecularly targeted therapy for this difficult-to-treat disease were based around the inhibition of gene products of the hypoxia-inducible factor (HIF) transcription factor (i.e., VEGF). Recent data suggest that inhibition of mTOR results in clinical benefit in patients with poor prognostic features, and in preclinical models this therapeutic effect involves downregulation of HIF. Intriguingly, patients with nonclear cell histology appeared to obtain clinical benefit when treated with mTOR inhibitors. This review will highlight the mTOR pathway, its relevance to both clear cell and nonclear cell renal cell carcinoma, and its place in the host of quickly expanding treatment options.
Hanna
Sara C
SC
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB 7295, Chapel Hill, NC 27599, USA. sara_hanna@med.unc.edu
Heathcote
Samuel A
SA
Kim
William Y
WY
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D051793:Hypoxia-Inducible Factor 1; D025521:Tumor Suppressor Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases