Tony Hunter

Tony Hunter was born in Ashford, Kent (United Kingdom) in August 1943. He graduated in 1966 from the University of Cambridge, where he also obtained his PhD. In 1975 he joined the Salk Institute, rising to a professorship in 1982. Since 1983, he has also held a professorship at the University of California, San Diego. He has headed the Salk Institute Cancer Center since 2008.

Author of almost 550 publications, he has held editorial posts with 26 journals, including Cell, Proceedings of the National Academy of Sciences and eLife.

Among his multiple distinctions, he is a fellow of the Royal Society, a member of the United States National Academy of Sciences and the Institute of Medicine of the National Academies, and Einstein Professor of the Chinese Academy of Sciences.

In the last ten years, oncologists’ pharmaceutical arsenal for the fight against cancer has been enlarged by some thirty drugs. New weapons whose power is measured in the years added to patients’ lives. The work of the three winners in the Biomedicine category in this seventh edition of the BBVA Foundation Frontiers of Knowledge Awards has been central to this advance: Tony Hunter, professor and Director of the Salk Institute Cancer Center; Joseph Schlessinger, Chairman of the Department of Pharmacology at Yale University School of Medicine; and Charles Sawyers, Human Oncology and Pathogenesis Program Chair at the Memorial Sloan Kettering Cancer Center. They are — in the words of the citation — “three eminent scientists who have taken the field all the way from initial basic discoveries to clinical applications that save lives.”

The drugs developed thanks to Hunter, Schlessinger and Sawyers have opened the door to personalized medicine. They are compounds that act specifically on the alterations causing cancer and not on healthy cells, so facilitate more effective treatments with fewer side effects.

Each laureate has his own chapter in the story, reflecting his own background and ambitions. Its starting point was an entirely chance discovery. Tony Hunter, a molecular biologist, began working in the mid 1960s. The object of his postdoctoral research in the Salk Institute, his career home, was of a purely basic nature: a small virus causing tumors in mice. Hunter was trying to find the protein that gave the virus this ability, but he was not alone in the search. One of his colleagues, it seemed, was further ahead. In trying to follow his steps, Hunter failed to spot that the pH buffer solution he was using in experiments was past its expiry date. And that was to prove a stroke of luck for medicine. For it turned out that the normal, unexpired solution was masking an unknown type of enzyme — tyrosine kinase — that only came to light through Hunter’s oversight.

The news spread fast around the world’s laboratories. Numerous teams repeated his experiments, deliberately using outdated buffers, and the tyrosine kinases were there for all to admire: a large protein family until that point indistinguishable from any other. This happened in 1979. And it was soon clear that the finding was important for cancer, as Schlessinger recalls: “Very quickly we found that tyrosine kinase receptors became mutated in cancer. So suddenly it was a big story.”

It was Joseph Schlessinger (Topusko, modern Croatia; 1945), a chemist by training with a PhD in biophysics from the Weizmann Institute of Science (Israel), who revealed the vital role played by tyrosine kinases: like a key they open a specific door in the cell membrane, inducing within a cascade of chemical signals that intervene in cell metabolism, proliferation and multiple other processes. Cancer appears when there are alterations in those chemical freeways connecting the cell’s exterior with its nucleus.

“We realized that if we could block these altered pathways, we would have new drugs to treat cancer,” explains Schlessinger, who has been behind the development of several such compounds. “Now there are maybe thirty cancer drugs based on this strategy, and they are much more selective and effective than conventional chemotherapy. Most of them cannot be considered a cure, but they do extend life expectancy, which is a real revolution.”

But much remains to be done: around a third of the R&D effort of the pharmaceutical industry is devoted to the search for new anti-tumor agents that inhibit tyrosine kinase activity. And one of the most urgent challenges is to overcome patient resistances to these drugs.

This, precisely, was the cause taken up by Charles L. Sawyers (Nashville, United States; 1959), a medical practitioner who switched into research due in part to the death of a young patient suffering chronic myeloid leukemia (CML). In 1998 Sawyers took part in human trials of the first tyrosine kinase targeted drug, imatinib, for the treatment of CML, with such good results that it was fast-tracked to approval in 2001.

But the news was not so good for all the patients included in the trial. Some who initially showed a spectacular improvement very soon relapsed, an experience Sawyers looks back on as “one of the most emotionally upsetting” of his career. Determined to find out why, he and his team came up with the answer: “We found additional mutations in the gene encoding the protein that imatinib targets. So, based on that, we developed another agent, desatinib, that inhibits the same protein but in a different way.” Desatinib was approved in 2006.

“These drugs have completely changed the approach of the entire pharma industry, at least in cancer,” Sawyers reflects. And the treatment protocol has changed in tandem: now the drug to be administered to each patient is determined by a previous genetic analysis. “We have identified hundreds of mutations, and have gone in a short time from having just imatinib to act on them to having dozens of different drugs. This breakthrough could never have happened without basic research, which has given us an understanding of the deep-seated mechanisms of cancer.”