2016
DOI: 10.1093/abbs/gmv103
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HER3/ErbB3, an emerging cancer therapeutic target

Abstract: HER3 is a member of the HER (EGFR/ErbB) receptor family consisting of four closely related type 1 transmembrane receptors (EGFR, HER2, HER3, and HER4). HER receptors are part of a complex signaling network intertwined with the Ras/Raf/MAPK, PI3K/AKT, JAK/STAT, and PKC signaling pathways. Aberrant activation of the HER receptors and downstream signaling molecules tips the balance on cellular events, leading to various types of cancers. Monoclonal antibodies (mAbs) and small molecule inhibitors targeting EGFR an… Show more

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Cited by 70 publications
(63 citation statements)
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“…Anti-HER2 antibodies such as Herceptin develop acquired resistance through a variety of mechanisms, including activation of tyrosine kinase in CSCs, upregulation of HER3, activating mutations in the p110a subunit of PIKK (PIK3CA), enhanced HER-ligand autocrine signaling and alterations in apoptotic pathways [69]. HER3 has now also been proposed as potentially driving survival of HER2+ cells once they have developed resistance to HER2 inhibitors such as lapatinib and trastuzumab [69].…”
Section: Use Of Multiple Mechanismsmentioning
confidence: 99%
“…Anti-HER2 antibodies such as Herceptin develop acquired resistance through a variety of mechanisms, including activation of tyrosine kinase in CSCs, upregulation of HER3, activating mutations in the p110a subunit of PIKK (PIK3CA), enhanced HER-ligand autocrine signaling and alterations in apoptotic pathways [69]. HER3 has now also been proposed as potentially driving survival of HER2+ cells once they have developed resistance to HER2 inhibitors such as lapatinib and trastuzumab [69].…”
Section: Use Of Multiple Mechanismsmentioning
confidence: 99%
“…Sequencing of all coding exons of ERBB3 identified specific somatic mutations in ERBB3, and expression of the ERBB3 mutants in breast epithelial cells led to oncogenic transformation in the presence of HER2 (129). Several investigational drugs at various stages of development have been described for ERBB3 (130), and whether the more recently identified ERBB3 mutations are sensitive to ERBB3 and/or HER2 targeted therapies remain to be addressed.…”
Section: 2 Her/erbb Familymentioning
confidence: 99%
“…Among four members of the HER family (EGFR, HER2, HER3 and HER4), HER3 is indicated to play an important role in HER signaling and drug resistance (19). With dimerization with EGFR or HER2, HER3 signals through phosphatidylinositol 3-kinase pathway (20,21).…”
Section: Introductionmentioning
confidence: 99%