This book exemplifies the evolution of oncogene HER2-encoded enzyme from its discovery to the stage of a fully recognized target for breast cancer therapy. Intensive research over the last three decades has uncovered major mechanisms that regulate the transformation of a normal tissue to a malignant tumor. However, to the disappointment of many molecular biologists, these significant advances in identifying oncogenes, tumor-suppressors and critical signalling pathways have generated only limited impact in clinical oncology. This frustration may not persist for long: tailor-made drugs developed specifically to recognize molecular targets, and intercept biochemical engines whose intricacy is well understood, are on the verge of revolutionizing contemporary medicine. The selection of chapters for this book is aimed at highlighting the intimate associations between basic and clinical research, which is essential for rational drug development. The wealth of data accumulated on the evolutionary origin of HER2 is reviewed. Signal transduction events elicited by stimulating HER2 are also described.
This topical field holds the promise of identifying critical biochemical reactions whose inhibition will abrogate the oncogenic action of HER2. Furthermore the book surveys prognostic correlates of HER2 with an emphasis on breast cancer and the importance of HER2 as a predictory of response to chemotherapy and hormonal therapy. The development of a monoclonal antibody to HER2 by Genentech Inc. is reviewed by some of the scientists involved. The authors detail the considerations they undertook when selecting a specific monoclonal antibody and tailoring it for clinical use. The potential involvement of several transcription regulators and their use in gene therapy targeted at HER2 are discussed as well. Being the first oncogene whose protein product has been targeted by therapy, HER2 offers a glimpse of the future of molecular medicine. If realized, the powerful potential of molecular biology will open new dimensions for targeted therapy of breast and other diseases.
Examples not only include vectors to deliver antisense reagents and ribozymes to block HER2 expression but also the use of combinatorial chemistry to generate antagonists of ligands upstream of HER2, as well as inhibitors of enzymes lying downstream of the oncoprotein.