Type

Journal Article

Authors

Robert O'Connor
Martin Clynes
Sandra Roche
Denis M Collins
Laura Breen
Gráinne Dunne

Subjects

Microbiology

Topics
protein kinase inhibitors carcinoma squamous cell genetics antineoplastic combined chemotherapy protocols lapatinib metabolism lung neoplasms adenocarcinoma quinazolines drug therapy administration dosage male epidermal growth factor gene expression regulation neoplastic pathology drug resistance neoplasm time factors pharmacology drug effects humans middle aged p glycoprotein cell line tumor dose response relationship drug

Modulation of P-gp expression by lapatinib. (2010)

Abstract Chemotherapy drug resistance is a major obstacle in the treatment of cancer. It can result from an increase in levels of cellular drug efflux pumps, such as P-glycoprotein (P-gp). Lapatinib, a growth factor receptor tyrosine kinase inhibitor, is currently in clinical trials for treatment of breast cancer. We examined the impact of co-incubation of chemotherapy drugs in combination with lapatinib in P-gp over-expressing drug resistant cells. Unexpectedly, lapatinib treatment, at clinically relevant concentrations, increased levels of the P-gp drug transporter in a dose- and time-responsive manner. Conversely, exposure to the epidermal growth factor (EGF), an endogenous growth factor receptor ligand, resulted in a decrease in P-gp expression. Despite the lapatinib-induced alteration in P-gp expression, use of accumulation, efflux and toxicity assays demonstrated that the induced alteration in P-gp expression by lapatinib had little direct impact on drug resistance.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

Robert O'Connor, Martin Clynes, Sandra Roche, Denis M Collins, Laura Breen, Gráinne Dunne

Experts in our system

1
Robert O'Connor
Dublin City University
Total Publications: 71
 
2
Martin Clynes
Dublin City University
Total Publications: 209
 
3
Sandra Roche
Dublin City University
Total Publications: 6
 
4
D M Collins
Dublin City University
Total Publications: 16
 
5
Laura Breen
Dublin City University
Total Publications: 11