After More Than 30 Years, Research on HER2 Continues to Expand Our Understanding of Cancer

Robert L. Ferris, MD, PhD

In reviewing the recent progress from the European Society of Medical Oncology Breast 2021 Virtual Congress, a number of abstracts presented data that focused on diagnostic, therapeutic, or other biological investigations around the HER2 receptor and its associated growth factor pathway. It struck me as exciting and gratifying for the fi eld of biologically driven, precision oncology that the discovery of such a marker protein, the HER2 receptor and the ErbB family, is still a major area of investigation and fruitful benefit in the clinic for patients.

The abstracts presented in this issue of Targeted Therapies in Oncology focus on neratinib (Nerlynx) as an irreversible HER2 inhibitor with therapeutic potential. Other research looked at the possibility of less intense trastuzumab (Herceptin), the anti-HER2 monoclonal antibody that has been approved for some decades, in the adjuvant setting.

Discoveries made in the mid-to-late 1980s by Drs Dennis Slamon and Stuart Aaronson involving the HER2 family have led to a number of advances: a subset of patients eligible for targeted therapies, biological tumor classification, and even antibody-drug conjugates, which deliver a payload using this targeted receptor for concentration of toxic chemotherapy. Indeed, genomic guidance based on mutations or copy number alterations is another way that we can diagnose and potentially track patients with circulating tumor DNA. So, looking back on the 30 to 40 years since the HER2 protein and its relevant oncogenic pathway were discovered, it is amazing that we are still actively investigating the therapeutic potential and the true evidence for precision oncology and biology-based cancer treatment.

It has taken some decades, but the identification of targets such as HER2 has enabled us to segregate cancers into different subtypes, develop novel therapeutic strategies, and eventually understand the biology distinguishing one group of patients from another. Furthermore, as we deploy our therapeutic weapons at the cancer cells, we need to have some specific target to shoot at—and this was one of the first. Understanding tumor heterogeneity and the role of individual pathways is commonplace now in the 2020s. However, thinking about how far we have come since the late 1980s reinforces that this is the correct path for translational science and many patients are benefiting. But what is equally intriguing is how much more we have to learn as clinical trials are still testing nuances of subgroups defined by HER2 in breast cancer and the ErbB family across many other solid tumors. The path is long, but progress is happening faster and faster.