Bench to Bedside

Lewis Cantley, PhD ’75, has been fascinated with understanding how things work ever since he was a boy in West Virginia, where his father taught him to make his own toys and design his own rockets. Weill Cornell's Lewis Cantley, PhD '75, is leading a revolution in cancer biology By Beth Saulnier Photographs by John […]

Lewis Cantley, PhD ’75, has been fascinated with understanding how things work ever since he was a boy in West Virginia, where his father taught him to make his own toys and design his own rockets.

Lewis Cantley

Weill Cornell's Lewis Cantley, PhD '75, is leading a revolution in cancer biology

By Beth Saulnier

Photographs by John Abbott

When Lewis Cantley was a boy growing up in West Virginia, he once asked his father if they could buy some fireworks for the Fourth of July. "Why do you want to buy firecrackers?" his father responded. "Go make your own." The senior Cantley gave his son the recipe for gunpowder, and young Lew went to work; before long, he'd graduated to building rockets. Similarly, Cantley's go-kart was a custom design, powered by a souped-up lawnmower engine—which the boy optimized after studying the vagaries of internal combustion. "From my earliest memories," says Cantley, PhD '75, "I was always extremely curious about how everything worked."

Cantley's father was largely self-educated. He didn't go to college, but he soaked up knowledge on a wide variety of topics, even reading the encyclopedia from A to Z. "He was in the Coast Guard during World War II, so he learned Morse code, which he taught me when I was quite young," recalls Cantley, now a professor of cancer biology at the Medical College. "He also learned a lot about navigation, the tides, what controlled the weather. So when I would ask a question like ‘Why does it rain?' instead of saying, ‘Because God makes it rain,' he would say, ‘Well, the moisture collects, it rises, gets to a high temperature, cools in the high atmosphere, causes drops of a certain size, and at some point the drops become so large that they begin to fall.' "

The family never bought toys. If Cantley admired a plaything that a kid down the street had, his father would show him how to build it—and the boy would pass the knowledge on to his friends. "By the time I was sixteen I could take a car engine completely apart and put it back together, and it would run," he says. "So that curiosity, and the confidence that I could figure out how anything worked, was what drove me. It also made me totally unafraid to ask questions about anything, because I figured I could understand it at some level."

Lewis Cantley

That mindset has served Cantley well over the past four decades. He's now one of the world's leading cancer researchers: the discoverer of a key pathway in cancer biology; leader of a $15 million Stand Up To Cancer "dream team"; winner of the most lucrative prize in biology and medicine. His recruitment from Harvard in fall 2012 was both a coup for Cornell and a vital step in the buildup of its bench-to-bedside research enterprise. "It was a huge splash around the country," Medical College Dean Laurie Glimcher says of Cantley's hiring. "I knew it was a great recruit, but I did not anticipate what a buzz would be created. It immediately raised the image of both Weill Cornell and NewYork-Presbyterian Hospital." John Leonard, associate dean for clinical research, lauds Cantley as not only a world-class scientist, but one who is intensely committed to bringing discoveries to the bedside. "It's remarkable how patient-focused he is," says Leonard, a professor of hematology and medical oncology. "Many people would be content to continue to write papers, win grants, and get acclaim, but he is focused on taking it to the next level—and always with an eye toward, ‘How are we ultimately going to use this to help patients?' "

For Cantley, the move offered not only the chance to get in on the ground floor of Weill Cornell's institutional revolution—a shift symbolized by the $650 million Belfer Research Building, which opened in January with his lab as its first occupant—but the opportunity to work in an intensely collaborative environment at a propitious moment: the dawn of truly personalized medicine. "Over the years, there has been a very fragmented approach to cancer," Cantley observes. "You have the basic scientists who know the pathways and understand the biology, the clinicians who treat the patients, and the pharma companies who make the drugs—and they're three completely isolated groups of people. We have to bring them all together as a team. So when you design a clinical trial, you have the basic scientists suggesting the biomarkers; you have a mechanism teasing out the mutations in each individual patient; and then, based on that, you put the patient on the right trial. This needs to be done in a seamless manner. And it's not done in a seamless manner anywhere—but the opportunity to do that here is better than at any other institution I know of."

Cantley's arrival roughly coincided with the founding of the Institute for Precision Medicine, a translational research hub the Medical College launched in early 2013 to offer targeted treatments based on a patient's genetic profile—including those whose disease is advanced or has become drug resistant. Among the key targets in personalized cancer medicine is an enzyme whose discovery established Cantley's scientific reputation two decades ago. Known as phosphoinositide 3-kinase (shortened as PI3-kinase or PI3K), it's a signaling pathway that plays an essential role in as many as 80 percent of cancers, including those of the breast, ovaries, and endometrium. "In addition to discovering the enzyme and its function, Dr. Cantley has been involved in figuring out which types of tumors commonly contain mutations of the gene that encodes PI3-kinase, and he is now developing clinical trials whereby individuals that have this type of mutation can be treated with PI3-kinase inhibitors," notes medicine professor Andrew Dannenberg, who has done extensive research on the connection between cancer and inflammation. "That's a remarkable odyssey and body of work—from discovering the gene to understanding its function to figuring out how it's regulated and what it controls downstream, all the way to determining its role in cancer and how often it's mutated, and providing the basis for personalized cancer investigation."

The PI3K pathway was the focus of the Stand Up To Cancer team that Cantley led, a sixty-researcher effort that wrapped up last October after four years. The work was also cited in the awarding of the first Breakthrough Prize in Life Sciences in February 2013. Cantley was one of eleven recipients of the prize, whose sponsors include founders of Google and Facebook—and which carries a $3 million award for each winner. That eye-popping amount (more than double that of the Nobel) initially prompted Cantley's wife to ask, "Are you sure this isn't a joke?" But no: the $3 million was indeed received—on his sixty-fourth birthday, no less.

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