The Role of Tumor-Associated Antigen HER2/neu in Tumor Development and the Different Approaches for Using It in Treatment: Many Choices and Future Directions

Abstract

The treatment of HER2-positive cancers has changed significantly over the past ten years thanks to a significant number of promising new approaches that have been added to our arsenal in the fight against cancer, including monoclonal antibodies, inhibitors of tyrosine kinase, antibody-drug conjugates, vaccination, and particularly, adoptive-T-cell therapy after its great success in hematological malignancies. Equally important is the new methodology for determining patients eligible for targeted HER2 therapy, which has doubled the number of patients who can benefit from these treatments. However, despite the initial enthusiasm, there are still several problems in this field represented by drug resistance and tumor recurrence that require the further development of new more efficient drugs. In this review, we discuss various approaches for targeting the HER2 molecule in cancer treatment, highlighting their benefits and drawbacks, along with the different mechanisms responsible for resistance to HER2-targeted therapies and how to overcome them.

Keywords: CAR-T cells; HER2; HER2-positive cancer; HER2-targeted immunotherapy; HER2-targeted vaccines; antibody–drug conjugates.

Figure 1

Mechanisms of action of some anti-HER2 therapies. Created with BioRender.com, accessed on 1 October 2022.