QnAs with Tony Hunter and James Allison.

In the mid-1990s, the miracle drug Gleevec revolutionized cancer treatment, offering terminally ill patients with chronic myeloid leukemia (CML) a new lease on life. Until then, the only weapons in the medical arsenal against cancer were the blunt and brutal triad of surgery, radiation, and conventional chemotherapy. Gleevec, which ushered in the era of molecularly targeted medicine, proved to be a broadsword with which to fight cancer. The drug was designed to block the action of a class of enzymes called tyrosine kinases, which activate signaling proteins by adding a phosphate tag to them. As their name suggests, tyrosine kinases attach phosphates to amino acids called tyrosines, and the phosphorylated proteins set off a cascade that turns cells cancerous. Salk Institute biochemist Tony Hunter discovered tyrosine phosphorylation in the late 1970s, publishing his findings in a pair of key articles in Cell (1) and PNAS (2). At the time, Hunter had nary a clue that his work would transform cancer treatment in less than two decades. “I didn’t set out to cure cancer, but that’s just the way things turned out,” recalls Hunter. Hunter’s discovery was not the only cancer breakthrough to mark the mid-1990s. When MD Anderson Cancer Center immunologist James Allison reported in Science (3) that the immune system can be trained to attack tumors by jamming its inbuilt brakes, it was hailed as a lapel-grabbing advance. The strategy, named checkpoint blockade, has yielded a handful of blockbuster drugs—Yervoy, Opdivo, Keytruda, Tecentriq—that have made cancer immunotherapy a frontline treatment for dozens of patients worldwide. Yet the question of why only some patients benefit from immunotherapy continues to puzzle researchers. With unbidden certainty, Allison prognosticates that an approach that combines immunotherapy with molecularly targeted drugs and radiation might help improve response rates in clinical trials. For their complementary efforts to combat a redoubtable foe, Hunter and Allison, bothmembers of theNational Academyof Sciences, were rewardedwith the 2017 inaugural Sjöberg Prize for cancer research by the Royal Swedish Academy of Sciences. PNAS spoke with the duo to mark the occasion.