Reference Detail

Request Content

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Ref Type Journal Article
PMID (29420467)
Authors Hyman DM, Piha-Paul SA, Won H, Rodon J, Saura C, Shapiro GI, Juric D, Quinn DI, Moreno V, Doger B, Mayer IA, Boni V, Calvo E, Loi S, Lockhart AC, Erinjeri JP, Scaltriti M, Ulaner GA, Patel J, Tang J, Beer H, Selcuklu SD, Hanrahan AJ, Bouvier N, Melcer M, Murali R, Schram AM, Smyth LM, Jhaveri K, Li BT, Drilon A, Harding JJ, Iyer G, Taylor BS, Berger MF, Cutler RE, Xu F, Butturini A, Eli LD, Mann G, Farrell C, Lalani AS, Bryce RP, Arteaga CL, Meric-Bernstam F, Baselga J, Solit DB
Title HER kinase inhibition in patients with HER2- and HER3-mutant cancers.
Journal Vol Issue Date Pages Journal Short Title
Nature 554 7691 2018 Feb 08 189-194 Nature
URL
Abstract Text Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, 'basket' trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials.gov identifier NCT01953926). Efficacy in HER2-mutant cancers varied as a function of both tumour type and mutant allele to a degree not predicted by preclinical models, with the greatest activity seen in breast, cervical and biliary cancers and with tumours that contain kinase domain missense mutations. This study demonstrates how a molecularly driven clinical trial can be used to refine our biological understanding of both characterized and new genomic alterations with potential broad applicability for advancing the paradigm of genome-driven oncology.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
ATR R1183Q missense unknown ATR R1183Q does not lie within any known functional domains of the Atr protein (UniProt.org). R1183Q has been identified in sequencing studies (PMID: 29420467, PMID: 30205045), but has not been biochemically characterized and therefore, its effect on Atr protein function is unknown (PubMed, May 2026).
ERBB3 E480Q missense unknown ERBB3 (HER3) E480Q lies within the extracellular domain of the Erbb3 (Her3) protein (UniProt.org). E480Q has been identified in sequencing studies (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb3 (Her3) protein function is unknown (PubMed, Jun 2026).
ERBB3 G233W missense unknown ERBB3 (HER3) G233W lies within the extracellular domain of the Erbb3 (Her3) protein (UniProt.org). G233W has been identified in sequencing studies (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb3 (Her3) protein function is unknown (PubMed, May 2026).
ERBB3 P306H missense unknown ERBB3 (HER3) P306H lies within the extracellular domain of the Erbb3 (Her3) protein (UniProt.org). P306H has been identified in sequencing studies (PMID: 29420467, PMID: 28487883), but has not been biochemically characterized and therefore, its effect on Erbb3 (Her3) protein function is unknown (PubMed, Jun 2026).
ERBB3 R667H missense unknown ERBB3 (HER3) R667H lies within the cytoplasmic domain of the Erbb3 (Her3) protein (UniProt.org). R667H has been identified in the scientific literature (PMID: 29963236, PMID: 29420467, PMID: 29718453), but has not been biochemically characterized and therefore, its effect on Erbb3 (Her3) protein function is unknown (PubMed, Jun 2026).
ERBB3 T355A missense unknown ERBB3 (HER3) T355A lies within the extracellular domain of the Erbb3 (Her3) protein (UniProt.org). T355A has been identified in the scientific literature (PMID: 29338072, PMID: 29967250, PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb3 (Her3) protein function is unknown (PubMed, Jan 2026).
JAK2 R487C missense unknown JAK2 R487C does not lie within any known functional domains of the Jak2 protein (UniProt.org). R487C has been identified in sequencing studies (PMID: 29420467, PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2026).
MST1R R396Q missense unknown MST1R R396Q lies within the Sema domain of the Mst1r protein (UniProt.org). R396Q has been identified in sequencing studies (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Mst1r protein function is unknown (PubMed, Mar 2026).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB3 mutant Advanced Solid Tumor no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in no objective response, a clinical benefit rate of 12.5% (2/16), and a median progression-free survival of 1.7 months in patients with advanced solid tumors harboring ERBB3 (HER3) mutations (PMID: 29420467; NCT01953926). 29420467