| Literature DB >> 25051360 |
Nicole M Davis1, Melissa Sokolosky1, Kristin Stadelman1, Steve L Abrams1, Massimo Libra2, Saverio Candido2, Ferdinando Nicoletti2, Jerry Polesel3, Roberta Maestro4, Antonino D'Assoro5, Lyudmyla Drobot6, Dariusz Rakus7, Agnieszka Gizak7, Piotr Laidler8, Joanna Dulińska-Litewka8, Joerg Basecke9, Sanja Mijatovic10, Danijela Maksimovic-Ivanic10, Giuseppe Montalto11, Melchiorre Cervello12, Timothy L Fitzgerald13, Zoya Demidenko14, Alberto M Martelli15, Lucio Cocco15, Linda S Steelman1, James A McCubrey1.
Abstract
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 be reviewed in association with suppression of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway.Entities:
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Year: 2014 PMID： 25051360 PMCID： PMC4148087 DOI： 10.18632/oncotarget.2209
Source DB: PubMed Journal: Oncotarget ISSN： 1949-2553