Combining an EGFR directed tyrosine kinase inhibitor with autophagy-inducing drugs: A beneficial strategy to combat non-small cell lung cancer

Yaara Gorzalczany, Yuval Gilad, Dina Amihai, Ilan Hammel, R. Sagi-Eisenberg Ronit, Ofer Merimsky

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The potential therapeutic value of combinatorial regimens based on an EGF receptor tyrosine kinase inhibitor (TKI) and autophagy inducing drugs was evaluated by comparing their molecular impacts on H1299 and A549 non-small cell lung cancer (NSCLC) cells, which overexpress wild type EGF receptor, but are either deficient or have wild type p53 alleles, respectively. We show that H1299 cells display a considerably lower sensitivity to erlotinib treatment, which can be restored by combining erlotinib with rapamycin or with imatinib, though to a lesser extent. Cytotoxicity was associated with increased autophagy and hyperpolarization of the mitochondrial membrane potential. Therefore, combining an EGF receptor directed TKI with an autophagy-inducing drug, preferably, rapamycin, might be beneficial in treating poor responding NSCLC patients.

Original languageEnglish
Pages (from-to)207-215
Number of pages9
JournalCancer Letters
Volume310
Issue number2
DOIs
StatePublished - 28 Nov 2011

Funding

FundersFunder number
Israeli Ministry of Health-The Chief Scientist’s Office
Maria Rossi Ascoli Fund

    Keywords

    • Autophagy
    • Erlotinib
    • NSCLC
    • Rapamycin
    • TKI

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