Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: Impact on future treatment strategies

Simonetta M. Leto, Livio Trusolino

Research output: Contribution to journalArticle

Abstract

Only approximately 10 % of genetically unselected patients with chemorefractory metastatic colorectal cancer experience tumor regression when treated with the anti-epidermal growth factor receptor (EGFR) antibodies cetuximab or panitumumab ("primary" or "de novo" resistance). Moreover, nearly all patients whose tumors initially respond inevitably become refractory ("secondary" or "acquired" resistance). An ever-increasing number of predictors of both primary and acquired resistance to anti-EGFR antibodies have been described, and it is now evident that most of the underlying mechanisms significantly overlap. By trying to extrapolate a unifying perspective out of many idiosyncratic details, here, we discuss the molecular underpinnings of therapeutic resistance, summarize research efforts aimed to improve patient selection, and present alternative therapeutic strategies that are now under development to increase response and combat relapse.

Original languageEnglish
Pages (from-to)709-722
Number of pages14
JournalJournal of Molecular Medicine
Volume92
Issue number7
DOIs
Publication statusPublished - 2014

Keywords

  • Anti-EGFR antibodies
  • Colorectal cancer
  • Primary resistance
  • Response biomarkers
  • Secondary resistance
  • Targeted therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)
  • Medicine(all)

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