Lapatinib potentiates cytotoxicity of  YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter

Research output: Contribution to journalJournal articlepeer-review

  • Branka Radic-Sarikas
  • Melinda Halasz
  • Kilian V M Huber
  • Georg E Winter
  • Kalliopi P Tsafou
  • Theodore Papamarkou
  • Brunak, Søren
  • Walter Kolch
  • Giulio Superti-Furga

Adverse side effects of cancer agents are of great concern in the context of childhood tumors where they can reduce the quality of life in young patients and cause life-long adverse effects. Synergistic drug combinations can lessen potential toxic side effects through lower dosing and simultaneously help to overcome drug resistance. Neuroblastoma is the most common cancer in infancy and extremely heterogeneous in clinical presentation and features. Applying a systematic pairwise drug combination screen we observed a highly potent synergy in neuroblastoma cells between the EGFR kinase inhibitor lapatinib and the anticancer compound YM155 that is preserved across several neuroblastoma variants. Mechanistically, the synergy was based on a lapatinib induced inhibition of the multidrug-resistance efflux transporter ABCB1, which is frequently expressed in resistant neuroblastoma cells, which allowed prolonged and elevated cytotoxicity of YM155. In addition, the drug combination (i.e. lapatinib plus YM155) decreased neuroblastoma tumor size in an in vivo model.

Original languageEnglish
JournalScientific Reports
Volume7
Issue number1
Pages (from-to)3091
ISSN2045-2322
DOIs
Publication statusPublished - 8 Jun 2017
Externally publishedYes

    Research areas

  • Journal Article

ID: 184322649