About this Research Topic

Background

Human Epidermal Growth Factor 2 (HER2) driven breast cancers are categorized into two subtypes, the first subtype, HER2-positive breast cancers and they are sensitive to HER2-targeted therapy. The second subtype, HER2-low breast cancer constitutes approximately, 60% of all breast cancers and express low levels of HER2, defined as a score of 1+ on Immunohistochemical (IHC) analysis or as an IHC score of 2+. Currently available HER2-directed therapies have been ineffective in patients with these “HER2-low” cancers. Genomics analysis has demonstrated that HER2-low breast cancer is a heterogeneous disease. Further, majority of HER2-low breast cancer patients have poor prognostic factors, such as larger tumor sizes, higher histological grades, and more regional lymph node involvement. Recently a HER2-Antibody-Drug-Conjugate (ADC), trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician’s choice of chemotherapy. These results have the potential to improve the treatment outcome for more than half of patients historically categorized as having HER2-negative breast cancer.

This Research Topic welcomes high quality Original Research Articles, Systematic Reviews, and Mini Reviews. Contributions should focus on HER2-low breast cancer, including, mechanistic underpinnings, therapeutic resistance, tumor heterogeneity, genomic landscape.

We will particularly welcome articles that emphasize on following topics:

• Challenges on detection and diagnosis of HER2-low breast cancer
• Underlying biology and signaling of HER2-low breast cancer
• Preclinical therapeutic resistance of HER2-ADC in HER1-low BC in vivo models
• Tumor heterogeneity
• Genomic landscape of HER2-low breast cancer
• Novel therapeutics, Bi-specific HER2 mAb discovery, CAR-T cell therapy, and preclinical validation
• Clinical implications of HER2 ADC in HER2-low breast cancer


Please note, manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.


Dr. Tarantino receives grants and remuneration from AstraZeneca.

Keywords: Bi-specific HER2 mAb discovery, CAR-T cell therapy, HER2-low breast cancer, detection, diagnosis, resistance of HER2-ADC, tumor heterogeneity

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