Targeted therapy in NSCLC driven by HER2 insertions
- PMID: 25806285
- PMCID: PMC4367663
- DOI: 10.3978/j.issn.2218-6751.2014.02.06
Targeted therapy in NSCLC driven by HER2 insertions
Abstract
HER2 mutations, largely exon 20 in-frame insertions, have been described as an oncogenic driver alteration in 1% to 4% of NSCLC, exclusively in adenocarcinoma histology. The prognostic implication of these alterations is not known. Phase I and II trial data suggest that afatinib, neratinib and dacomitinib have some activity in this molecular subgroup. No comparative data, or any data regarding the activity of pertuzumab or trastuzumab-emtansine is available. HER2 deregulation either by protein overexpression or gene amplification, has little clinical relevance to date, as trials investigating trastuzumab activity merely suggest a benefit in the very small minority of patients whose tumor highly overexpresses HER2, a subpopulation that amounts to 2% to 6% of mostly adenocarcinomas.
Keywords: HER2 mutations; afatinib; dacomitinib; irreversible pan HER-receptor inhibitor; lung cancer.
References
-
- Pao W, Hutchinson KE. Chipping away at the lung cancer genome. Nat Med 2012;18:349-51. - PubMed
-
- Spector NL, Blackwell KL. Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 2009;27:5838-47. - PubMed
-
- Ferguson KM, Berger MB, Mendrola JM, et al. EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Mol Cell 2003;11:507-17. - PubMed
-
- Ross JS, Slodkowska EA, Symmans WF, et al. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 2009;14:320-68. - PubMed
-
- Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376:687-97. - PubMed
Publication types
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous