Next-generation mTOR inhibitors in clinical oncology

How pathway complexity informs therapeutic strategy

Seth A. Wander, Bryan T. Hennessy, Joyce M Slingerland

Research output: Contribution to journalArticle

285 Citations (Scopus)

Abstract

Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.

Original languageEnglish
Pages (from-to)1231-1241
Number of pages11
JournalJournal of Clinical Investigation
Volume121
Issue number4
DOIs
StatePublished - Apr 1 2011

Fingerprint

Medical Oncology
Sirolimus
Phosphatidylinositol 3-Kinases
DNA Damage
Neoplasms
Cell Survival
Phosphotransferases
Therapeutics
Cell Proliferation
Food
Growth

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Next-generation mTOR inhibitors in clinical oncology : How pathway complexity informs therapeutic strategy. / Wander, Seth A.; Hennessy, Bryan T.; Slingerland, Joyce M.

In: Journal of Clinical Investigation, Vol. 121, No. 4, 01.04.2011, p. 1231-1241.

Research output: Contribution to journalArticle

@article{effe874935d4419ca5c5594e943c691b,
title = "Next-generation mTOR inhibitors in clinical oncology: How pathway complexity informs therapeutic strategy",
abstract = "Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.",
author = "Wander, {Seth A.} and Hennessy, {Bryan T.} and Slingerland, {Joyce M}",
year = "2011",
month = "4",
day = "1",
doi = "10.1172/JCI44145",
language = "English",
volume = "121",
pages = "1231--1241",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "4",

}

TY - JOUR

T1 - Next-generation mTOR inhibitors in clinical oncology

T2 - How pathway complexity informs therapeutic strategy

AU - Wander, Seth A.

AU - Hennessy, Bryan T.

AU - Slingerland, Joyce M

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.

AB - Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.

UR - http://www.scopus.com/inward/record.url?scp=79953298958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953298958&partnerID=8YFLogxK

U2 - 10.1172/JCI44145

DO - 10.1172/JCI44145

M3 - Article

VL - 121

SP - 1231

EP - 1241

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 4

ER -