[PI3K-AKT-mTOR pathway: Description, therapeutic development, resistance, predictive/prognostic biomarkers and therapeutic applications for cancer]

Thibault Brotelle; Jacques-Olivier Bay

doi:10.1016/j.bulcan.2015.09.011

[PI3K-AKT-mTOR pathway: Description, therapeutic development, resistance, predictive/prognostic biomarkers and therapeutic applications for cancer]

Bull Cancer. 2016 Jan;103(1):18-29. doi: 10.1016/j.bulcan.2015.09.011. Epub 2015 Nov 12.

[Article in French]

Authors

Thibault Brotelle¹, Jacques-Olivier Bay²

Affiliations

¹ CHU Estaing-Clermont-Ferrand, service d'hématologie clinique adulte et de thérapie cellulaire, 1, place Lucie-et-Raymond-Aubrac, 63003 Clermont-Ferrand cedex 01, France. Electronic address: [email protected].
² CHU Estaing-Clermont-Ferrand, service d'hématologie clinique adulte et de thérapie cellulaire, 1, place Lucie-et-Raymond-Aubrac, 63003 Clermont-Ferrand cedex 01, France.

PMID: 26582734
DOI: 10.1016/j.bulcan.2015.09.011

Abstract

Among many cancer cells signaling pathways, PI3K-AKT-mTOR plays a major role in growth, proliferation and cellular survival. This is a complex pathway activated either by an extracellular way (receptors with tyrosine kinase activity) or by an intracellular way with transformed or overexpressed proteins involved in the signal transduction. To date, there are many applications of mTOR inhibitors in oncology with an expanding development rapidly. However, resistances appear to mTOR inhibitors which lead to 2nd generation mTOR inhibitors development. A better knowledge of predictive and prognostic biomarkers will allow to specify the group of patients who may benefit from these treatments and help to the choice.

Keywords: Biomarker; Everolimus; Inhibiteur mTOR; Marqueur biologique; PI3K-AKT-mTOR; Resistance; Résistance; Temsirolimus; mTOR inhibitor; Évérolimus.

Publication types

Review

MeSH terms

Antineoplastic Agents / therapeutic use*
Apoptosis
Biomarkers, Tumor / physiology
Breast Neoplasms / drug therapy
Cell Proliferation
Cell Survival
Drug Resistance, Neoplasm*
Enzyme Activation
Enzyme Inhibitors / therapeutic use
Female
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
Lymphoma, Mantle-Cell / drug therapy
Lymphoma, Non-Hodgkin / drug therapy
Neoplasms / blood supply
Neoplasms / drug therapy*
Neoplasms / enzymology
Neovascularization, Pathologic / etiology
Neuroendocrine Tumors / drug therapy
Phosphatidylinositol 3-Kinases / physiology
Phosphoinositide-3 Kinase Inhibitors*
Prognosis
Protein-Tyrosine Kinases / antagonists & inhibitors*
Protein-Tyrosine Kinases / physiology
Signal Transduction
TOR Serine-Threonine Kinases / antagonists & inhibitors*
TOR Serine-Threonine Kinases / physiology
Tuberous Sclerosis / drug therapy

Substances

Antineoplastic Agents
Biomarkers, Tumor
Enzyme Inhibitors
Phosphoinositide-3 Kinase Inhibitors
MTOR protein, human
Protein-Tyrosine Kinases
TOR Serine-Threonine Kinases