Molecular Targets and Angiogenesis in Renal Cell Carcinoma, A Multitarget Approach: Mini Review

Curr Drug Targets. 2017;18(10):1204-1213. doi: 10.2174/1389450117666160502152518.

Abstract

Background: Renal cell carcinoma (RCC) accounts for 2% of all adult malignancies and is associated with a case fatality rate as high as 40%. RCC has been on the rise for the last 6 decades at a steady increase of 2% per annum. Much work has been done to uncover the pathogenesis of the disease and the role of angiogenesis has been a recurrent denominator connected to vascular endothelial growth factor (VEGF) and its downstream effectors along with the mammalian target of rapamycin (mTOR) mediated signal transduction pathway.

Objective: This review will discuss relevant inhibitors of key biomarkers to the disease in hopes of paving the way for novel treatments geared towards improving RCC morbidity and mortality rates.

Results and conclusion: Currently, treatment of advanced RCC includes one or more of the following: partial or radical nephrectomy, systemic therapy, immunotherapy and targeted therapy. Still drug resistance continues to be a challenge to many of the approved drugs and those undergoing clinical trials. However, the inclusion of targeted therapies has improved advanced RCC treatment success rates over that of surgery alone, and over that of the use of traditional chemotherapy for this relatively chemo-resistant disease. In an era of personalized medicine, research utilizing a polypharmacology approach could enhance efficacy of drug leads to treating RCC.

Keywords: Mammalian target of rapamycin; angiogenesis; multi target approach; personalized medicine; renal cell carcinoma; vascular endothelial growth factor.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / metabolism
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Molecular Targeted Therapy
  • Precision Medicine
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Angiogenesis Inhibitors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MTOR protein, human
  • TOR Serine-Threonine Kinases