“Probably the most significant and different component of this article versus other reviews was our attempt to push the thinking in the field to the next level.”

The ErbB receptors have been in the spotlight of cancer research for many years. In particular, their role in a common type of cancer—e.g., breast cancer—and the association of their deregulated activity with a poor patient prognosis have made them targets of first choice for pharmaceutical companies. Moreover, even after two decades of intense research, new underlying molecular mechanisms, cellular and physiological roles, and new targeting approaches continue to be uncovered. This constellation makes the ErbB field interesting, challenging, and dynamic, and thereby interesting for a large audience of scientists in basic research and physicians involved in patient care. Our review provides a concise and readable overview of this large research area.

This is a review article summarizing the most important and recent findings in the field, putting emphasis on more than just one dimension of the ErbB world. Covered topics include an overview of the signaling complexity at the molecular level, the description of the "bigger" phenotypic appearances during various stages of development, and a deep dive into the involvement in cancer progression and, importantly, how selective targeting is being successfully applied in various therapeutic approaches.

When writing this review article, we tried to accomplish these following three goals:

1. Provide a comprehensive and exhaustive review on the most important findings during the 20-year-long research in the ErbB field.
2. Show how the ever-increasing knowledge of ErbB signaling led to a relatively precise understanding at the molecular level of processes involved in human tumorigenesis and how this made it possible to selectively target these "altered" cellular players and processes to successfully combat disease progression.
3. Probably the most significant and different component of this article versus other reviews was our attempt to push the thinking in the field to the next level. To accomplish this we focused in part on clinical efficacy and side effects of compounds in clinical trials and how these aspects could be linked to molecular characteristics. By taking a step back from the ultimate detail and trying to understand interactions and networks at a broader level, it is likely that, in a hopefully not-too-distant future, additional molecular markers will be identified that will enable a specific therapy design with the highest benefit and lowest side effects at the single-patient level.

Dr. Nancy Hynes has been interested in breast cancer research for many years. As a post-doctoral fellow at the Swiss Cancer Institute in Lausanne, she entered the field by studying a virus that causes mammary cancer in mice, the Mouse Mammary Tumor Virus. A few years later she turned her attention to human breast cancer and her lab was one of the first to discover that the gene encoding the ErbB2 receptor tyrosine kinase was amplified in ~25% of primary human breast tumors. Since that time she has devoted herself to understanding the mechanisms underlying the oncogenic potential of ErbB2 as well as developing cancer therapies that target this receptor. Dr. Thomas Holbro joined the lab of Dr. Hynes for his Ph.D., driven by his interest in research on a medically relevant field, in particular, cancer. His aim was always to see a potential application of the research results in terms of a new target or new diagnostic marker to improve therapeutic approaches.