Targeting HER2 genomic alterations in non-small cell lung cancer

Oncogenic mutations and amplifications in the erythroblastic oncogene B (ERBB2), or human epidermal growth factor receptor 2 (HER2), have emerged as distinct oncogenic drivers and drug targets in non-small cell lung cancer (NSCLC). Each genomic alteration occurs in 2–4% of NSCLC by next generation s...

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Autores principales:	Jie Zeng, Weijie Ma, Richard Benjamin Young, Tianhong Li
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	HER2 ERBB2 Genomic alterations Biomarkers Non-small cell lung cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/3f40bb24885440a89ee50c2dc8b49f30
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spelling	oai:doaj.org-article:3f40bb24885440a89ee50c2dc8b49f302021-12-01T05:06:41ZTargeting HER2 genomic alterations in non-small cell lung cancer2667-005410.1016/j.jncc.2021.04.001https://doaj.org/article/3f40bb24885440a89ee50c2dc8b49f302021-06-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S266700542100017Xhttps://doaj.org/toc/2667-0054Oncogenic mutations and amplifications in the erythroblastic oncogene B (ERBB2), or human epidermal growth factor receptor 2 (HER2), have emerged as distinct oncogenic drivers and drug targets in non-small cell lung cancer (NSCLC). Each genomic alteration occurs in 2–4% of NSCLC by next generation sequencing and is associated with constitutive HER2 activation. The most common HER2 mutations in NSCLC are exon 20 mutation A775_G776insYVMA mutation in the kinase domain and S310F mutation in the extracellular domain. Unlike in breast and gastric cancer, HER2 protein overexpression in NSCLC is not validated to be a biomarker predictive of clinical response to HER2-targeted agents. High HER2 protein overexpression by immunohistochemistry (3+) only occurs in 2–4% of NSCLC. Until now HER2-targeted agents (such as afatinib and ado-trastuzumab emtansine) only demonstrate modest clinical activity in patients with HER2-mutant NSCLC. Retrospective studies show concern for inferior clinical benefit of immune checkpoint inhibitors in HER2-mutated NSCLC. Therefore, platinum-based chemotherapy with or without an anti-angiogenesis inhibitor remains the first line standard treatment for this patient population. In May 2020 trastuzumab deruxtecan (T-DXd) received the U.S. Food and Drug Administration breakthrough therapy designation for HER2-mutant metastatic NSCLC, and was added as an option for HER2-mutant NSCLC to the NCCN guidelines V1.2021. A global phase III study of pyrotinib compared to docetaxel as a second line therapy for advanced NSCLC harboring HER2 exon 20 mutations was just opened for enrollment in September 2020. In this review, we highlight the current knowledge and perspectives on targeting-HER2 genomic alterations in NSCLC.Jie ZengWeijie MaRichard Benjamin YoungTianhong LiElsevierarticleHER2ERBB2Genomic alterationsBiomarkersNon-small cell lung cancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of the National Cancer Center, Vol 1, Iss 2, Pp 58-73 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HER2 ERBB2 Genomic alterations Biomarkers Non-small cell lung cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	HER2 ERBB2 Genomic alterations Biomarkers Non-small cell lung cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jie Zeng Weijie Ma Richard Benjamin Young Tianhong Li Targeting HER2 genomic alterations in non-small cell lung cancer
description	Oncogenic mutations and amplifications in the erythroblastic oncogene B (ERBB2), or human epidermal growth factor receptor 2 (HER2), have emerged as distinct oncogenic drivers and drug targets in non-small cell lung cancer (NSCLC). Each genomic alteration occurs in 2–4% of NSCLC by next generation sequencing and is associated with constitutive HER2 activation. The most common HER2 mutations in NSCLC are exon 20 mutation A775_G776insYVMA mutation in the kinase domain and S310F mutation in the extracellular domain. Unlike in breast and gastric cancer, HER2 protein overexpression in NSCLC is not validated to be a biomarker predictive of clinical response to HER2-targeted agents. High HER2 protein overexpression by immunohistochemistry (3+) only occurs in 2–4% of NSCLC. Until now HER2-targeted agents (such as afatinib and ado-trastuzumab emtansine) only demonstrate modest clinical activity in patients with HER2-mutant NSCLC. Retrospective studies show concern for inferior clinical benefit of immune checkpoint inhibitors in HER2-mutated NSCLC. Therefore, platinum-based chemotherapy with or without an anti-angiogenesis inhibitor remains the first line standard treatment for this patient population. In May 2020 trastuzumab deruxtecan (T-DXd) received the U.S. Food and Drug Administration breakthrough therapy designation for HER2-mutant metastatic NSCLC, and was added as an option for HER2-mutant NSCLC to the NCCN guidelines V1.2021. A global phase III study of pyrotinib compared to docetaxel as a second line therapy for advanced NSCLC harboring HER2 exon 20 mutations was just opened for enrollment in September 2020. In this review, we highlight the current knowledge and perspectives on targeting-HER2 genomic alterations in NSCLC.
format	article
author	Jie Zeng Weijie Ma Richard Benjamin Young Tianhong Li
author_facet	Jie Zeng Weijie Ma Richard Benjamin Young Tianhong Li
author_sort	Jie Zeng
title	Targeting HER2 genomic alterations in non-small cell lung cancer
title_short	Targeting HER2 genomic alterations in non-small cell lung cancer
title_full	Targeting HER2 genomic alterations in non-small cell lung cancer
title_fullStr	Targeting HER2 genomic alterations in non-small cell lung cancer
title_full_unstemmed	Targeting HER2 genomic alterations in non-small cell lung cancer
title_sort	targeting her2 genomic alterations in non-small cell lung cancer
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/3f40bb24885440a89ee50c2dc8b49f30
work_keys_str_mv	AT jiezeng targetingher2genomicalterationsinnonsmallcelllungcancer AT weijiema targetingher2genomicalterationsinnonsmallcelllungcancer AT richardbenjaminyoung targetingher2genomicalterationsinnonsmallcelllungcancer AT tianhongli targetingher2genomicalterationsinnonsmallcelllungcancer
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Targeting HER2 genomic alterations in non-small cell lung cancer

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