EGFR inhibitor-mediated apoptosis in solid tumors

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The epidermal growth factor receptor (EGFR) plays an important role in the development and progression of solid tumors. Growing evidence suggests that EGFR activation also mediates resistance to chemotherapy and radiation therapy. Studies elucidating the biochemical basis of these observations have demonstrated that EGFR inhibition down-modulates mitogen-activated protein kinase (MAPK) or PI3-K/Akt-dependent survival pathways in many tumor types and is associated with a proapoptotic shift in Bcl-2 expression and/or activation. Although research to date has focused on well-characterized survival pathways, other pathways in the complex EGFR signaling network may also be involved in tumor survival. Whereas suppressing EGFR signaling may be insufficient to fully induce apoptosis, it may prime neoplastic cells for apoptosis induced by other cytotoxic stimuli. Preclinical and clinical data show that inhibition of EGFR, together with enhanced induction of apoptosis, may counter resistance to chemotherapy and radiation therapy, both of which have been shown to induce EGFR-dependent survival responses. Further study of EGFR-modulated apoptotic pathways may facilitate the rational development of improved combination regimens.

Original languageEnglish (US)
Pages (from-to)305-320
Number of pages16
JournalJournal of Experimental Therapeutics and Oncology
Volume6
Issue number4
StatePublished - 2007

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Epidermal Growth Factor Receptor
Apoptosis
Neoplasms
Radiotherapy
Drug Therapy
Mitogen-Activated Protein Kinases
Research

Keywords

  • Apoptosis
  • Apoptotic pathways
  • EGFR inhibition
  • EGFR-inhibitor therapy
  • EGFR-targeted therapy
  • Tumor survival

ASJC Scopus subject areas

  • Pharmacology
  • Cancer Research

Cite this

EGFR inhibitor-mediated apoptosis in solid tumors. / Goel, Sanjay; Hidalgo, Manuel; Perez-Soler, Roman.

In: Journal of Experimental Therapeutics and Oncology, Vol. 6, No. 4, 2007, p. 305-320.

Research output: Contribution to journalArticle

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