Combination of epidermal growth factor receptor inhibitors and antiangiogenic drugs: A model for treatment

Erika Martinelli, Teresa Troiani, Floriana Morgillo, Maria Carmela Piccirillo, Katia Monaco, Maria Pia Morelli, Tina Cascone, Fortunato Ciardiello

Research output: Contribution to journalArticlepeer-review

Abstract

The epidermal growth factor receptor (EGFR) autocrine pathway plays a crucial role in human cancer since it contributes to relevant processes in tumor development and progression, including cell proliferation, regulation of apoptotic cell death, angiogenesis and metastatic spread. EGFR-blocking monoclonal antibodies and small-molecule EGFR tyrosine kinase inhibitors have been developed as anticancer drugs. Although anti-EGFR agents are active in a subset of cancer patients, constitutive resistance in a large number of patients and the development of acquired resistance in initially responding patients are a relevant clinical issue. A major problem is that intrinsic and/or acquired resistance can occur, and it could be due to the activation of alternative cancer cell growth controlling pathways. One mechanism linked to acquired resistance to EGFR-inhibitor treatment, in particular, is the activation of uncontrolled, tumor-induced angiogenesis through an increase in vascular endothelial growth factor (VEGF) secretion by cancer cells. Significant and sustained antitumor activity in this context can be obtained by combining selective anti-EGFR drugs with antiangiogenic agents. In this review, we focus on the preclinical and clinical evidence showing that an approach combining anti-EGFR and antiangiogenic drugs is feasible and could represent a paradigm for a rational combined multi-targeted treatment of cancer.

Original languageEnglish
Pages (from-to)123-129
Number of pages7
JournalTargeted Oncology
Volume1
Issue number3
DOIs
Publication statusPublished - Jul 2006

Keywords

  • Bevacizumab
  • Cetuximab
  • Epidermal growth factor receptor
  • Erlotinib
  • Molecular targeted therapy
  • Vascular endothelial growth factor receptor
  • ZD6474

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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