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Review
. 2023 Dec 29;14(1):64.
doi: 10.3390/life14010064.

HER2 Alterations in Non-Small Cell Lung Cancer: Biologico-Clinical Consequences and Interest in Therapeutic Strategies

Emma Loeffler  1 , Julien Ancel  1   2 , Véronique Dalstein  1   3 , Gaëtan Deslée  1   2 , Myriam Polette  1   3 , Béatrice Nawrocki-Raby  1
Affiliations
Review

HER2 Alterations in Non-Small Cell Lung Cancer: Biologico-Clinical Consequences and Interest in Therapeutic Strategies

Emma Loeffler et al. Life (Basel). .

Abstract

Lung cancer stands as the first cause of death by cancer in the world. Despite the improvement in patients' outcomes in the past decades through the development of personalized medicine approaches, a substantial portion of patients remains ineligible for _targeted therapies due to the lack of a "druggable" molecular _target. HER2, a receptor tyrosine kinase member of the EGFR/ErbB family, is known to show oncogenic properties. In this review, we focus on the different HER2 dysregulation mechanisms that have been observed in non-small cell lung cancer (NSCLC): gene mutation, gene amplification, protein overexpression and protein hyper-phosphorylation, the latter suggesting that HER2 dysregulation can occur independently of any molecular aberration. These HER2 alterations inevitably have consequences on tumor biology. Here, we discuss how they are not only involved in abnormal proliferation and survival of cancer cells but also potentially in increased angiogenic properties, mesenchymal features and tumor immune escape. Finally, we review the impact of these HER2 alterations in various therapeutic approaches. While standard chemotherapy and groundbreaking immunotherapy seem rather ineffective for HER2-altered NSCLCs, the development of HER2-_targeted therapies such as tyrosine kinase inhibitors, anti-HER2 antibodies and especially antibody-drug conjugates could provide new hopes for patients.

Keywords: HER2 alterations; anti-HER2 _targeted therapy; non-small cell lung cancer; oncogenic drivers.

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Conflict of interest statement

M.P. and B.N-R. are the inventors in the patent application WO 2018/055023—Methods and pharmaceutical compositions for the treatment of lung cancer. The remaining authors declare no conflicts of interest.

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