Cancer combination therapy of the sesquiterpenoid artesunate and the selective EGFR-tyrosine kinase inhibitor erlotinib

Abstract

Background: The shift from cytotoxic to targeted chemotherapy led to improved treatment outcomes in oncology. Nevertheless, many cancer patients cannot be cured from their disease because of the development of drug resistance and side effects.

Purpose: There is an ongoing quest for novel compounds, which raised not only the interest in natural products but also in novel combination therapy regimens.

Study design: In this review, we report on the inhibition epidermal growth factor receptor (EGFR) by targeted small molecules and their combination with natural products from medicinal plants.

Results: The combination of erlotinib with artesunate leads to synergistic inhibition of cell growth in isobologram analyses. Artesunate is an approved anti-malaria drug, which is also active against cancer as shown in vitro, in vivo and in preliminary clinical phase I/II trials.

Conclusion: The combination of natural products (e.g. the sesquiterpenoid artesunate) and synthetic compounds (e.g. the small molecule EGFR tyrosine kinase inhibitor erlotinib) may lead to improved clinical success rates in oncology.

Keywords: Cancer; Natural products; Small molecule inhibitors; Synergy.