The role of mTOR inhibitors and P13K pathway blockade in RCC

Michel Choueiri, Philip Mack

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The mammalian target of rapamycin (mTOR) is an important intermediary of the signaling transduction cascade that reacts to external nutrient abundance, to external growth factor and hormonal signaling, and to internal cellular energy levels. There are two major complexes formed with mTOR: mTORC1 and mTORC2. mTORC1 is rapamycin (also known as sirolimus) sensitive, and acts as a signaling intermediary for nutrient availability, energy levels, and growth factor signaling. mTORC2 is less well defined, and is capable of upregulating AKT activity. Two mammalian targets of rapamycin (mTOR) inhibitors were FDA approved for use in renal cell carcinoma (RCC) in the past 5 years. Temsirolimus, an intravenous sirolimus ester was shown to improve overall survival in a study of 626 patients with untreated metastatic RCC and poor risk features. Everolimus, an oral rapamycin analog, was shown to improve progression-free survival compared to placebo in patients with metastatic RCC who progressed on sorafenib, sunitinib, or both. New agents are being investigated that function upstream of mTOR to block activity of phosphoinositide-3 phosphate kinase (PI3K), AKT, or are capable of blocking mTORC1 and mTORC2 simultaneously.

Original languageEnglish (US)
Title of host publicationKidney Cancer: Principles and Practice
PublisherSpringer Berlin Heidelberg
Pages209-224
Number of pages16
ISBN (Electronic)9783642218583
ISBN (Print)9783642218576
DOIs
StatePublished - Jan 1 2012

    Fingerprint

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Choueiri, M., & Mack, P. (2012). The role of mTOR inhibitors and P13K pathway blockade in RCC. In Kidney Cancer: Principles and Practice (pp. 209-224). Springer Berlin Heidelberg. https://doi.org/10.1007/978-3-642-21858-3_14