The Role of HER2 Mutant Alleles in Breast Cancer


“Our research study has demonstrated that poziotinib is highly potent in neratinib-resistant HER2 L755S lobular and ductal breast cancer models [...].”


BUFFALO, NY- November 6, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on October 31, 2023, entitled, “The uncharted role of HER2 mutant alleles in breast cancer.”


Somatic HER2 mutations are a novel class of therapeutic targets across different cancer types. Treatment with the tyrosine kinase inhibitor (TKI) neratinib as a single agent continues to be evaluated in HER2-mutant metastatic disease. However, responses are heterogeneous, with frequent early progression. 


In this new editorial, researchers Rashi Kalra, Bora Lim, Matthew J. Ellis, and Shyam M. Kavuri from Baylor College of Medicine discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.


“In summary, preclinical findings described above support clinical investigation of poziotinib in a subset of ER + mBC harboring HER2 somatic mutations and suggest further studies to evaluate poziotinib as a therapeutic agent in additional tumor types.”


Read the full paper: DOI: https://doi.org/10.18632/oncotarget.28489 


Correspondence to: Shyam M. Kavuri


Email: [email protected] 


Keywords: metastasis, poziotinib, HER2, neratinib, invasive lobular breast carcinoma



About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open-access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.


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