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

Phytomedicine. 2017 Dec 15:37:58-61. doi: 10.1016/j.phymed.2017.11.003. Epub 2017 Nov 10.

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.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Artemisinins / administration & dosage
  • Artemisinins / pharmacology*
  • Artesunate
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride / administration & dosage
  • Erlotinib Hydrochloride / pharmacology
  • Humans
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Artemisinins
  • Artenimol-R
  • Protein Kinase Inhibitors
  • Artesunate
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors