Combination of anti-EGFR drugs with anti-angiogenic or other signal transduction inhibitors as a rational approach to cancer therapy

Maria P. Morelli, Jennifer Spratlin, S. Gail Eckhardt

Research output: Contribution to journalReview article

Abstract

Activation of the epidermal growth factor receptor (EGFR)-dependent intracellular signaling pathway has a relevant role in the development and the progression of several human cancers. However, EGFR-targeted therapies have a significant clinical activity only in a subgroup of cancer patients whose tumors express the EGFR. This is due in part to the activation of several other signal transduction pathways which will be EGFR-independent and could be responsible for cancer cell growth. A clinically relevant field of research is the development of rational, biologically based multi-targeted therapy combinations which will block cancer cell escape from single target inhibition, such as the use of EGFR inhibitors in monotherapy. A number of clinical trials with EGFR inhibitors in combination with classic cytotoxic agents have been undertaken with both interesting and disappointing results. It is, therefore, felt that combinations of EGFR inhibitors and other novel agents, which is based on the mechanistic knowledge of complementary signaling pathways whose concerted inhibition would efficiently block cancer cell growth, is the rationale therapeutic approach. Some of these pathways [i.e., mammalian target of rapamycin (mTOR), vascular endothelial growth factor receptor (VEGFR), ras/mitogen-activated protein kinase (MAPK) signaling, or insulin like growth factor receptor (IGFR)] which are functionally related to the activity of the EGFR will be discussed in this review to provide a scientific rationale for the combination of drugs which target these pathways with anti-EGFR agents.

Original languageEnglish (US)
Pages (from-to)284-291
Number of pages8
JournalCurrent Cancer Therapy Reviews
Volume3
Issue number4
DOIs
StatePublished - Nov 1 2007

Fingerprint

Angiogenesis Inhibitors
Epidermal Growth Factor Receptor
Signal Transduction
Neoplasms
Therapeutics
Somatomedin Receptors
Vascular Endothelial Growth Factor Receptor
Cytotoxins
Drug Combinations
Sirolimus
Growth
Mitogen-Activated Protein Kinases
Clinical Trials

Keywords

  • Anti-angiogenic drugs
  • EGFR inhibitors
  • Signal transduction
  • VEGF

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

Cite this

Combination of anti-EGFR drugs with anti-angiogenic or other signal transduction inhibitors as a rational approach to cancer therapy. / Morelli, Maria P.; Spratlin, Jennifer; Eckhardt, S. Gail.

In: Current Cancer Therapy Reviews, Vol. 3, No. 4, 01.11.2007, p. 284-291.

Research output: Contribution to journalReview article

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