HER2 and lung cancer

Abstract

In non-small-cell lung cancer (NSCLC), the identification of oncogenic driver mutations led to the definition of different clinical entities with different therapeutic opportunities, as demonstrated in patients harboring EGF receptor (EGFR) mutations or anaplastic lymphoma kinase translocations. Human EGFR2 (or HER2) has an established role as a prognostic and predictive factor in breast cancer. Although HER2 deregulation, including overexpression, amplification and mutation, has been described in NSCLC, its role as a therapy biomarker remains undefined. In the last few years, there has been a growing interest on HER2 mutation, with few anecdotal or retrospective studies suggesting a relevant role for this biomarker. This review discusses the prognostic and predictive impact of HER2 deregulation and the clinical implications of anti-HER2 strategies in NSCLC.

Keywords::

• anti-HER2 therapy
• EGFR
• HER2
• NSCLC
• oncogenic driver

Financial & competing interests disclosure

Supported in part by the Italian Association for Cancer Research (AIRC) and Associazione Oncologia Traslazionale (AOT). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Oncogenic driver mutations identify different lung cancers subtypes.

• • In non-small-cell lung cancer (NSCLC), HER2 is one of the more interesting biomarkers that is considered to play a central role in cancer proliferation.

• • HER2 is overexpressed, amplified or mutated in a significant fraction of lung adenocarcinomas.

• • The prognostic significance of HER2 dysregulation remains undefined.

• • HER2 gene copy number seems to affect sensitivity to anti-EGFR agents.

• • HER2 amplification is one of the mechanisms responsible for acquired resistance to reversible EGF receptor-tyrosine kinase inhibitors (EGFR-TKIs).

• • A combination of anti-EGFR and anti-HER2 agents should be considered in order to overcome acquired resistance to reversible EGFR-TKIs.

• • Anti-HER2 agents, and in particular the combination of trastuzumab and chemotherapy, seem effective in HER2 mutant NSCLC.

• • Systematic genotyping testing should include detection of HER2 mutations.