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Modulation of P-gp expression by lapatinib

Gráinne Dunne1, Laura Breen, Denis M Collins

  • 1National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland.

Investigational New Drugs
|July 8, 2010
PubMed

Insights

Lapatinib, used in breast cancer treatment, unexpectedly increased P-glycoprotein (P-gp) drug transporter levels in resistant cells. However, this did not significantly impact chemotherapy drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Chemotherapy drug resistance is a significant challenge in cancer therapy.
  • Increased expression of drug efflux pumps, like P-glycoprotein (P-gp), contributes to this resistance.
  • Lapatinib is an investigational tyrosine kinase inhibitor for breast cancer.

Purpose of the Study:

  • To investigate the effect of lapatinib on P-gp expression in drug-resistant cancer cells.
  • To determine if lapatinib affects chemotherapy drug resistance in P-gp over-expressing cells.

Main Methods:

  • Co-incubation of P-gp over-expressing cells with chemotherapy drugs and lapatinib.
  • Dose- and time-response studies of lapatinib on P-gp levels.
  • Accumulation, efflux, and toxicity assays to assess drug resistance.
  • Comparison with the effect of epidermal growth factor (EGF) on P-gp.

Main Results:

  • Lapatinib treatment increased P-gp transporter levels in a dose- and time-dependent manner.
  • Epidermal growth factor (EGF) exposure decreased P-gp expression.
  • Despite increased P-gp levels, lapatinib showed minimal direct impact on overall drug resistance.

Conclusions:

  • Lapatinib can upregulate P-gp expression in resistant cancer cells.
  • This lapatinib-induced increase in P-gp does not significantly alter chemotherapy drug resistance.
  • Further research is needed to understand the complex interactions between lapatinib and drug efflux pumps.

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