Dr. Tony Hunter, Dr. Brian J. Druker, and Dr. John Mendelsohn are the recipients of the 2018 Tang Prize in Biopharmaceutical Science. These three renowned American scholars are awarded for the discovery of protein tyrosine phosphorylation and tyrosine kinases as oncogenes, leading to successful targeted cancer therapies.
Dr. Tony Hunter, Professor of Biology at the Salk Institute, is the British-American scientist who discovered tyrosine phosphorylation and that the oncogene Src is a tyrosine kinase (TK). This discovery is nothing less than saying Dr. Hunter gave birth to the field of tyrosine kinase inhibitors (TKIs), which are prototypes of targeted cancer therapies. Its emergence made a milestone of cancer therapy.
Dr. Hunter’s discovery in 1979 at the Salk Institute paved the road for the next twenty years’ active research on tyrosine kinase oncogenes, leading to the development of TKIs (tyrosine kinase inhibitors). The field is still going strong almost forty years after his discovery. He also showed that cancer cells are highly tyrosyl-phosphorylated, indicating a close relationship between tyrosine phosphorylation and the uncontrollable growth of cancer cell. With his colleague, Bart Sefton, Dr. Hunter developed anti-phosphotyrosine antibodies, a very powerful tool for studying cancer signals and identifying TKIs. Thus, it is no exaggeration to say Dr. Tony Hunter opened up the “tyrosine kinase field” and brought forth the golden era of signal transduction research. The current success of targeted therapy owes a great deal to him.
Dr. Brian Druker, Director of Oregon Health Sciences University Knight Cancer Institute, is the physician scientist who led the successful clinical trial of imatinib (Gleevec®) on chronic myelogenous leukemia (CML). The disease that used to be treated by bone marrow transplantation is now curable by orally administrated drugs. Gleevec® increases patients’ survival rate from 50% to 90%. It’s been considered the most successful targeted cancer therapy drug in the 21st century and was approved for clinical use by the US FDA in 2001.
Gleevec® was the first successful example of tyrosine kinase-targeted therapy by small molecule inhibitors (TKIs). Now there are more than 29 TKIs which have been approved for clinical use. Clearly, Dr. Druker’s first successful trials heralded this still burgeoning targeted therapy era. Dr. Druker’s contributions are in both the development and application of TKI.
Dr. John Mendelsohn, President Emeritus of MD Anderson Cancer Center, took another approach while at UC San Diego working with Dr. Gordon Sato. They conceived the idea that antibodies targeting epidermal growth factor receptor (EGFR) may be an effective strategy for cancer treatment. EGFR is the prototype of receptor tyrosine kinases, located on the cell surface and a main engine to drive cell growth. It is often overexpressed or mutated to become oncogenic in different types of cancer, for example, breast cancer, lung cancer, colorectal cancer, ovarian cancer, bladder cancer, head/neck cancer, and esophageal cancer.
Dr. Mendelsohn and his team conducted preclinical research and proceeded to develop the anti-EGFR antibody cetuximab (Erbitux®). His effort to promote it into clinics eventually won the approval of the US FDA for the treatment of colon cancer and head/neck cancer. This was the first clinically approved therapy based on receptor tyrosine kinase-targeting antibody and a trail-blazer which has spurred many others to follow.
In summary, the discovery of protein tyrosine phosphorylation and tyrosine kinases sowed the seed for research in the ensuing forty years leading to a thorough understanding of the fundamental principles of cell growth and cancer development. The development of tyrosine kinase-targeted therapies has fundamentally changed the practices of cancer clinics. It provides great benefits to patients who suffer from this dreadful disease and gives hope that cancer can eventually be treated. The contributions of this years’ Tang Prize in Biopharmaceutical Science awardees to science and society are immeasurable. Their accomplishments amply illustrate how brilliant basic science can lead to clinical applications that benefit all mankind.
