Genomic alterations of ERBB receptors in cancer: Clinical implications

Rosalin Mishra, Ariella B. Hanker, Joan T. Garrett

Research output: Contribution to journalReview article

31 Citations (Scopus)

Abstract

The ERBB family of receptor tyrosine kinases has been implicated in carcinogenesis for over three decades with rigorous attention to EGFR and HER2. ERBB receptors, consisting of EGFR, HER2, HER3, and HER4 are part of a complicated signaling network that activates downstream signaling pathways including PI3K/ AKT, Ras/Raf/MAPK, JAK/STAT and PKC. It is well established that EGFR is amplified and/or mutated in gliomas and non-small-cell lung carcinoma while HER2 is amplified and/or over-expressed in breast, gastric, ovarian, non-small cell lung carcinoma, and several other tumor types. With the advent of next generation sequencing and large scale efforts to explore the entire spectrum of genomic alterations involved in human cancer progression, it is now appreciated that somatic ERBB receptor mutations occur at relatively low frequencies across multiple tumor types. Some of these mutations may represent oncogenic driver events; clinical studies are underway to determine whether tumors harboring these alterations respond to small molecule EGFR/HER2 inhibitors. Recent evidence suggests that some somatic ERBB receptor mutations render resistance to FDA-approved EGFR and HER2 inhibitors. In this review, we focus on the landscape of genomic alterations of EGFR, HER2, HER3 and HER4 in cancer and the clinical implications for patients harboring these alterations.

Original languageEnglish (US)
Pages (from-to)114371-114392
Number of pages22
JournalOncotarget
Volume8
Issue number69
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Neoplasms
Non-Small Cell Lung Carcinoma
Mutation
Receptor Protein-Tyrosine Kinases
Phosphatidylinositol 3-Kinases
Glioma
Stomach
Carcinogenesis
Breast
Clinical Studies

Keywords

  • EGFR
  • HER2
  • HER3
  • HER4
  • Mutation

ASJC Scopus subject areas

  • Oncology

Cite this

Genomic alterations of ERBB receptors in cancer : Clinical implications. / Mishra, Rosalin; Hanker, Ariella B.; Garrett, Joan T.

In: Oncotarget, Vol. 8, No. 69, 01.01.2017, p. 114371-114392.

Research output: Contribution to journalReview article

Mishra, Rosalin ; Hanker, Ariella B. ; Garrett, Joan T. / Genomic alterations of ERBB receptors in cancer : Clinical implications. In: Oncotarget. 2017 ; Vol. 8, No. 69. pp. 114371-114392.
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