Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention
2014
Autori:
Davis, Nicole M.Sokolosky, Melissa
Stadelman, Kristin
Abrams, Stephen L.
Libra, Massimo
Candido, Saverio
Nicoletti, Ferdinando
Polesel, Jerry
Maestro, Roberta
D'Assoro, Antonino
Drobot, Lyudmyla
Rakus, Dariusz
Gizak, Agnieszka
Laidler, Piotr
Dulinska-Litewka, Joanna
Basecke, Joerg
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Montalto, Giuseppe
Cervello, Melchiorre
Fitzgerald, Timothy L.
Demidenko, Zoya N.
Martelli, Alberto M.
Cocco, Lucio
Steelman, Linda S.
McCubrey, James A.
Tip dokumenta:
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
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.
Ključne reči:
Targeted Therapy; Therapy Resistance; Mutations; rapamycinIzvor:
Oncotarget, 2014, 5, 13, 4603-4650
DOI: 10.18632/oncotarget.2209
ISSN: 1949-2553
PubMed: 25051360