TY - JOUR
T1 - Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer
T2 - Possibilities for therapeutic intervention
AU - Davis, Nicole M.
AU - Sokolosky, Melissa
AU - Stadelman, Kristin
AU - Abrams, Steve L.
AU - Libra, Massimo
AU - Candido, Saverio
AU - Nicoletti, Ferdinando
AU - Polesel, Jerry
AU - Maestro, Roberta
AU - D'Assoro, Antonino
AU - Drobot, Lyudmyla
AU - Rakus, Dariusz
AU - Gizak, Agnieszka
AU - Laidler, Piotr
AU - Dulinska-Litewka, Joanna
AU - Basecke, Joerg
AU - Mijatovic, Sanja
AU - Maksimovic-Ivanic, Danijela
AU - Montalto, Giuseppe
AU - Cervello, Melchiorre
AU - Fitzgerald, Timothy L.
AU - Demidenko, Zoya N.
AU - Martelli, Alberto M.
AU - Cocco, Lucio
AU - Steelman, Linda S.
AU - McCubrey, James A.
PY - 2014
Y1 - 2014
N2 - The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance and metastasis. The expression of this pathway is frequently altered in breast cancer due to mutations at or aberrant expression of: HER2, ERalpha, BRCA1, BRCA2, EGFR1, PIK3CA, PTEN, TP53, RB as well as other oncogenes and tumor suppressor genes. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway and upstream HER2 has been associated with breast cancer initiating cells (CICs) and in some cases resistance to treatment. The anti-diabetes drug metformin can suppress the growth of breast CICs and herceptin-resistant HER2+ cells. This review will discuss the importance of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway primarily in breast cancer but will also include relevant examples from other cancer types. The targeting of this pathway will be discussed as well as clinical trials with novel small molecule inhibitors. The targeting of the hormone receptor, HER2 and EGFR1 in breast cancer will reviewed in association with suppression of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway.
AB - The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance and metastasis. The expression of this pathway is frequently altered in breast cancer due to mutations at or aberrant expression of: HER2, ERalpha, BRCA1, BRCA2, EGFR1, PIK3CA, PTEN, TP53, RB as well as other oncogenes and tumor suppressor genes. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway and upstream HER2 has been associated with breast cancer initiating cells (CICs) and in some cases resistance to treatment. The anti-diabetes drug metformin can suppress the growth of breast CICs and herceptin-resistant HER2+ cells. This review will discuss the importance of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway primarily in breast cancer but will also include relevant examples from other cancer types. The targeting of this pathway will be discussed as well as clinical trials with novel small molecule inhibitors. The targeting of the hormone receptor, HER2 and EGFR1 in breast cancer will reviewed in association with suppression of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway.
KW - MTOR
KW - Mutations
KW - PI3K
KW - Rapamycin
KW - Targeted therapy
KW - Therapy resistance
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UR - http://www.scopus.com/inward/citedby.url?scp=84904968175&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.2209
DO - 10.18632/oncotarget.2209
M3 - Article
C2 - 25051360
AN - SCOPUS:84904968175
SN - 1949-2553
VL - 5
SP - 4603
EP - 4650
JO - Oncotarget
JF - Oncotarget
IS - 13
ER -