mTOR pathway in renal cell carcinoma

Expert Rev Anticancer Ther. 2008 Feb;8(2):283-92. doi: 10.1586/14737140.8.2.283.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / mortality
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Drug Delivery Systems
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1 / genetics
  • Hypoxia-Inducible Factor 1 / metabolism
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / mortality
  • Male
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Prognosis
  • Risk Assessment
  • Sensitivity and Specificity
  • Signal Transduction
  • Survival Analysis
  • TOR Serine-Threonine Kinases
  • Treatment Outcome
  • Tumor Suppressor Proteins / antagonists & inhibitors*
  • Tumor Suppressor Proteins / metabolism

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Carrier Proteins
  • Hypoxia-Inducible Factor 1
  • Tumor Suppressor Proteins
  • Phosphotransferases (Alcohol Group Acceptor)
  • MTOR protein, human
  • TOR Serine-Threonine Kinases