Tang Prize Lecture
Saturday April 04, 2020
Sponsored by Experimental Biology
The Tang Prize in Biopharmaceutical Science recognizes original biopharmaceutical or biomedical research that has led to significant advances towards preventing, diagnosing and/or treating major human diseases to improve human health.
The 2020 Tang Prize Lecture at EB will be given by Tony Hunter, PhD, Professor of Biology at the Salk Institute for Biological Studies.
Tyrosine kinase inhibitors (TKIs) are the prototypes of targeted therapies, which already have significant impacts on the treatment of cancer patients. Dr. Hunter gave birth to this field by discovering tyrosine phosphorylation and that the oncogene src is a tyrosine kinase. At that time, it was already known that kinases are enzymes that can attach phosphates on the amino acids serine and threonine of a protein, but the discovery that tyrosine could also be phosphorylated revealed a brand new level of cellular regulation critically involved in development and disease. In the human genome, the tyrosine kinase family represents a minor class of protein kinases, but they are a major family of oncogenes (cancer-inducing genes). This is because many of them are receptors on the cell surface and are critically involved in transmitting signals to instruct cells to grow in response to environmental cues such as growth factors. Upon mutations, they become constitutively active and no longer require environmental cues to trigger a response. Cells would then grow incessantly, eventually becoming malignant.
As demonstrated later, shutting off the oncogenic tyrosine kinase signals by small molecules or antibodies indeed stops cancer cell growth and is an effective way to treat cancers. Mutated or activated tyrosine kinases have become superb diagnosis and prognosis markers for cancer. In addition to growth, tyrosine kinases are now found to function in cell migration, survival and other malignant phenotypes. Dr. Hunter’s discovery in 1979 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, and with his colleague, Bart Sefton, 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.
Tyrosine Phosphorylation - From Discovery to Drug Development and Beyond
- Salk Institute for Biological Studies