About this Medicine article

Targeting c-Met in triple negative breast cancer: preclinical studies using the c-Met inhibitor, Cpd A by Breen, Laura; Gaule, Patricia B.; Canonici, Alexandra; Walsh, Naomi; Collins, Denis M.; Cremona, Mattia; Hennessy, Bryan T.; Duffy, Michael J.; Crown, John; Donovan, Norma Oâ; Eustace, Alex J. is a Medicine article available to read on EtoBox.

Introduction Triple negative breast cancer (TNBC) represents a heterogeneous subtype of breast cancer that carries a poorer prognosis. There remains a need to identify novel drivers of TNBC, which may represent targets to treat the disease. c-Met overexpression is linked with decreased survival and is associated with the basal subtype of breast cancer. Cpd A, a kinase inhibitor selective/specific for Met kinase has demonstrated preclinical anti-cancer efficacy in TNBC. We aimed to assess the anti-cancer efficacy of Cpd A when combined with Src kinase, ErbB-family or hepatocyte growth factor (HGF) inhibitors in TNBC cell lines. Methods We determined the anti-proliferative effects of Cpd A, rilotumumab, neratinib and saracatinib tested alone and in combination in a panel of TNBC cells by acid phosphatase assays. We performed reverse phase protein array analysis of c-Met and IGF1Rβ expression and phosphorylation of c-Met (Y1234/1235) in TNBC cells and correlated their expression/phosphorylation with Cpd A sensitivity. We examined the impact of Cpd A, neratinib and saracatinib tested alone and in combination on invasive potential and colony formation.Results TNBC cells are not inherent

Author

Breen, Laura; Gaule, Patricia B.; Canonici, Alexandra; Walsh, Naomi; Collins, Denis M.; Cremona, Mattia; Hennessy, Bryan T.; Duffy, Michael J.; Crown, John; Donovan, Norma Oâ; Eustace, Alex J.

Publisher

Springer US; Springer-Verlag; Kluwer Academic Publishers; Springer Science and Business Media LLC (ISSN 0167-6997)

Published

2020

Language

EN

Field

Medicine (Health Sciences)