Targeted therapies for treatment of renal cell carcinoma: recent advances and future perspectives

Cancer Chemother Pharmacol. 2015 Aug;76(2):219-33. doi: 10.1007/s00280-015-2770-3. Epub 2015 May 12.

Abstract

Purpose: A wide variety of targeted therapies are available for the treatment of renal cancer that has progressed beyond the point at which surgery is a viable option. In addition, there are many more that are in the different stages of clinical trials. Here, we provide a methodical discussion of the efficacy and safety of targeted therapies for the treatment of advanced renal cell carcinoma.

Methods: We conducted a systematic literature employing the search terms: renal cell carcinoma targets, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and each of the drugs discussed within these papers.

Results: The identified targeted therapies work by disrupting specific signalling pathways involved in tumour progression, such as those responsible for angiogenesis and cell proliferation. Tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors are now established classes of drugs used in the treatment of renal cancer, with a total of six having received regulatory approval to date (sorafenib, sunitinib, pazopanib, axitinib, temsirolimus, and everolimus). Ongoing trials are likely to result in addition to these in the near future, for example, tivozanib, dovitinib, and cediranib. Furthermore, in addition to these small molecule drugs, immunotherapies involving monoclonal antibodies against signalling molecules such as vascular endothelial growth factor (bevacizumab) or programmed death-1 (nivolumab) are receiving increasing attention.

Conclusions: Targeted therapies have great potential for disrupting tumour progression by inhibiting certain signalling pathways. As our understanding of the biochemical pathways involved in cancer progresses, additional targets are certain to become apparent, expanding treatment options even further.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / blood supply
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Humans
  • Molecular Targeted Therapy
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Protein-Tyrosine Kinases
  • TOR Serine-Threonine Kinases