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Review
. 2024 Feb;10(2):113-123.
doi: 10.1016/j.trecan.2023.11.001. Epub 2023 Nov 25.

Targeting HER2 heterogeneity in breast and gastrointestinal cancers

Carmine Valenza  1 , Lorenzo Guidi  1 , Elena Battaiotto  1 , Dario Trapani  1 , Andrea Sartore Bianchi  2 , Salvatore Siena  2 , Giuseppe Curigliano  3
Affiliations
Review

Targeting HER2 heterogeneity in breast and gastrointestinal cancers

Carmine Valenza et al. Trends Cancer. 2024 Feb.

Abstract

About 20% of breast and gastric cancers and 3% of colorectal carcinomas overexpress the human epidermal growth factor receptor 2 (HER2) and are sensitive to HER2-directed agents. The expression of HER2 may differ within the same tumoral lesion (spatial intralesional heterogeneity), from different tumor locations (spatial interlesional heterogeneity), and throughout treatments (temporal heterogeneity). Spatial and temporal heterogeneity may impact on response and resistance to HER2-targeting agents and its prevalence and predictive role changes across HER2-overexpressing solid tumors. Therefore, the definition and the characterization of HER2 heterogeneity pose many challenges and its implementation as a reproducible predictive biomarker would help in guiding treatment modulation.

Keywords: HER2 heterogeneity; breast cancer; colorectal cancer; gastric cancer; human epidermal growth factor receptor 2.

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Conflict of interest statement

Declaration of interests G.C. reports honoraria for speaker's engagement: Roche, Seattle Genetics, Novartis, Lilly, Pfizer, Foundation Medicine, NanoString, Samsung, Celltrion, BMS, MSD; honoraria for providing consultancy: Roche, Seattle Genetics, NanoString; honoraria for participating in Advisory Board: Roche, Lilly, Pfizer, Foundation Medicine, Samsung, Celltrion, Mylan; honoraria for writing engagement: Novartis, BMS; honoraria for participation in Ellipsis Scientific Affairs Group; institutional research funding for conducting Phase 1 and 2 clinical trials: Pfizer, Roche, Novartis, Sanofi, Celgene, Servier, Orion, AstraZeneca, Seattle Genetics, AbbVie, Tesaro, BMS, Merck Serono, Merck Sharp Dohme, Janssen-Cilag, Philogen, Bayer, Medivation, Medimmune. All the competing interests were outside the submitted work. S.S. is advisory board member for Agenus, AstraZeneca, Bayer, BMS, CheckmAb, Daiichi-Sankyo, GSK, MSD, Merck, Novartis, Pierre-Fabre, Seagen, and T-One Therapeutics; A.S-B. reports honoraria for speaker's engagement: Amgen, Bayer, Guardant Health, Pierre-Fabre and Servier; honoraria for providing consultancy: Bayer, Novartis, Servier; all the competing interests were outside the submitted work. All other authors have no potential conflict of interest to disclose.

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