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Targeting the PI3K/Akt/mTOR Pathway for Breast Cancer Therapy

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Recent advances in genetics and genomics have revealed new pathways that are aberrantly activated in many breast cancers. Chief among these genetic changes are somatic mutations and/or gains and losses of key genes within the phosphoinositide 3-kinase (PI3K) pathway. Since breast cancer cell growth and progression is often dependent upon activation of the PI3K pathway, there has been intense research interest in finding therapeutic agents that can selectively inhibit one or more constituents of this signaling cascade. Here we review key molecules involved with aberrant PI3K pathway activation in breast cancers and current efforts to target these components for therapeutic gain.

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Abbreviations

4E-BP1:

eIF4E-binding protein

Akt/PKB:

protein kinase B

AMPK:

AMP-activated protein kinase

CNS:

central nervous system

DNA-PK:

DNA-dependent protein kinase

EGFR:

epidermal growth factor receptor

ER:

estrogen receptor alpha

FDG:

fluorodeoxyglucose

FGF:

fibroblast growth factor

FISH:

fluorescence in situ hybridization

FKBP12:

FK506-binding protein

GPCR:

G-protein-coupled receptors

HER2:

human epidermal growth factor receptor 2

IGF-1R:

insulin-like growth factor-1 receptor

ILK:

integrin-linked kinase

IRS-1:

insulin receptor substrate 1

miRNAs:

microRNAs

mTOR:

mammalian target of rapamycin

PARP:

poly(ADP-ribose) polymerase

PDK-1:

3’-phosphoinositide-dependent kinase 1

PET:

positron emission tomography

PH:

plextrin homology

PI3K:

phosphoinositide 3-kinase

PI(3,4,5)P3 :

phosphatidylinositol-3,4,5-trisphosphate

PR:

progesterone receptor

Pten:

phosphatase and tensin homologue deleted on chromosome 10

pTyr:

phosphotyrosine

RBD:

Ras Binding Domain

Redd1:

regulated in development and DNA damage response 1

Rheb:

Ras homolog enriched in brain

RTK:

receptor tyrosine kinase

SERD:

selective estrogen receptor down-regulator

SERM:

selective estrogen receptor modulator

SH2:

Src homology 2

Tsc:

tuberous sclerosis complex

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  1. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Rm 151, Baltimore, MD, 21287, USA

    Justin Cidado & Ben Ho Park

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Cidado, J., Park, B.H. Targeting the PI3K/Akt/mTOR Pathway for Breast Cancer Therapy. J Mammary Gland Biol Neoplasia 17, 205–216 (2012). https://doi.org/10.1007/s10911-012-9264-2

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