mTOR-blocking agents in advanced renal cancer: an emerging therapeutic option.

Abstract

BACKGROUND:

The mammalian target of rapamycin (mTOR) pathway inhibition has emerged as one of the main directions for the development of new targeted agents in renal cell carcinoma (RCC). A prominent member in its class of medications, temsirolimus has already been shown to improve overall survival in advanced kidney cancer, when compared with the previous standard, IFN-alpha.

OBJECTIVE:

The aim of this study was to review the most relevant preclinical and clinical data on the mTOR inhibitors, both in clinical use or in current development.

METHODS:

The authors give a comprehensive review of the existing English literature on the role of the mTOR pathway in renal tumorigenesis, as well as a detailed safety and efficacy analysis of older and newer rapamycin analogs.

RESULTS/CONCLUSIONS:

Rapamycin derivatives temsirolimus and everolimus have significant clinical activity in patients with advanced-stage RCC. Both parenteral and oral formulations of mTOR inhibitors have shown clinical efficacy and are currently being developed. Combinations of mTOR inhibitors with VEGF/VEGFR-blocking agents are also being studied, in an attempt to further enhance the antineoplastic effect.

• Authors: Constantin A Dasanu, Bernard A Clark 3rd, Doru T Alexandrescu
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 18 Issue 2 Pg. 175-87 (Feb 2009) ISSN: 1744-7658 [Electronic] England
• PMID: 19236264 (Publication Type: Journal Article, Review)

Chemical References

• Antibiotics, Antineoplastic
• Antineoplastic Agents
• Protein Kinases
• MTOR protein, human
• TOR Serine-Threonine Kinases
• Sirolimus

Topics

• Animals
• Antibiotics, Antineoplastic (pharmacology, therapeutic use)
• Antineoplastic Agents (adverse effects, pharmacology, therapeutic use)
• Carcinoma, Renal Cell (drug therapy)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Humans
• Hypophosphatemia (chemically induced)
• Kidney Neoplasms (drug therapy)
• Protein Kinases (drug effects, physiology)
• Signal Transduction (drug effects, physiology)
• Sirolimus (analogs & derivatives, pharmacology, therapeutic use)
• TOR Serine-Threonine Kinases