Source: forbes.com
Author: Thomas Stossel

This year’s Lasker Foundation annual prize for medical breakthroughs–the American version of the Nobel Prize–recognizes a breakthrough cancer treatment that has revolutionized chemotherapy, a “targeted therapy for chronic myelogenous leukemia.” But more symbolic–and no doubt controversial–was to whom the prize was awarded: two academic scientists and a former drug company employee.

Ironically, the treatment probably shouldn’t exist. Only 3,000 chronic myelogenous leukemia (CML) patients are diagnosed in the U.S. every year, a population usually thought too small to justify the hundreds of millions of dollars that companies must spend to develop new medicines. That the therapy exists at all is a testament to the dedication of our research community and the vital collaboration between academic and commercial scientists.

The Lasker prize for CML is viewed as the first practical payoff from decades of research attempting to understand why some cells deviate from their normal programming to become life-threatening cancer.

It has long been known that cancer cells multiply and spread wildly to destroy healthy tissues. The research that led to the new treatment revealed that in cancer cells a component of the signaling system controlling cell behavior performs autonomously, like a traffic light permanently set on green, instructing cells to multiply and uncontrollably invade nearby tissues. Researchers speculated that by shutting down the abnormal signals (switching the light from green to red) cancer cells, lacking the key signal to multiply, would behave normally.

This approach is a radical departure from 50 years of cancer treatment protocols based on ridding the body of all cancer cells–an approach known as “slash, burn and poison.” If surgical removal or the killing of cancer cells by radiation fails before they spread, the last resort is poisoning them with chemotherapy.

Chemotherapy kills rapidly multiplying cells, and it works–but at a price. Normal cells such as skin, hair, gastrointestinal and blood cells also multiply rapidly. Chemotherapy’s side effects therefore include baldness and dangerous infections due to lack of infection-fighting white blood cells. Suppressing cancer cells’ lethal behavior by “targeting” their abnormal machinery, rather than by brute force eradication, might improve patients’ chances of surviving with the disease and actually make life more tolerable than trying to eliminate the disease would.

The Lasker Award winners have contributed to validating this containment strategy, enabling the introduction of two drugs “targeted” against the green light that causes CML that lack most of chemotherapy’s toxicity. Taken life-long by patients, these drugs prevent CML from progressing. According to the prize announcement, the winners applied accumulated knowledge generated from cancer research to achieve this stunning advance.

But this account represents only part of the story and obscures a second reason the award is so richly deserved. The CML treatment story is a testimony not only to the difficulty of developing new treatments for complex diseases, but to the essential collaboration between academic physicians and researchers and private industry. Indeed, half of the Lasker awards over the past decade recognized major scientific contributions from pharmaceutical or medical device companies. Unfortunately critics have demonized this collaboration and imposed barriers to prevent “financial conflicts of interest” that will make such collaborations harder in the future.

Imatinib, which goes by the brand name Gleevec, the first of the two CML drugs, was produced by what is now Novartis. It was initially designed to block a target completely unrelated to CML. Subsequent testing revealed that the drug actually inhibits multiple reactions inside cells. One of these, however, was the CML target, and the persistent efforts of Lasker Awardee Brian Druker, an academic physician, to show that Gleevec shut down the destructive behavior of CML cells in the laboratory eventually overcame skepticism about its lack of specific targeting and led to testing Imitinab in CML patients.

Druker’s key partner and a champion of his work inside Novartis was co-prizewinner Nicholas Lydon, a Novartis biochemist, who participated in Gleevec’s development and provided Druker with it for the research on CML cells and (eventually) for a successful clinical trial.

To perform the trial, however, Druker and Lydon had to overcome Novartis’ concerns that the CML market was too small. Had another cancer-targeting product in Novartis’ pipeline thought to have more widespread applicability not had a formulation problem, Gleevec may never have been launched. More important, the key trial might not have occurred because of conflict of interest regulations now enforced at most academic health centers that could have forced Druker and Lydon to cease their collaboration.

Unexpectedly, Novartis’ legitimate concerns about the market for Gleevec turned out to be moot. Not only did the substantial survival benefits of Gleevec increase the size of the CML population, but another academic physician, George Demetri, capitalized on its lack of target specificity to try it “off-label” on patients with disseminated gastrointestinal stromal tumor (GIST), an even less treatable disease than CML prior to introduction of Imitinab.

Sustained remissions and even apparent cures of GIST led physicians to apply Gleevec successfully in diseases related to its other cellular targets. Among these are disorders unrelated to cancer such as complications of kidney failure.

All said and done, Gleevec is a “targeted therapy,” but it is hardly specific, and nobody can say for sure why it is so effective and relatively benign. However much we might yearn for clear rationales to drive medical progress, only the willingness of entrepreneurial physicians and researchers to resist conventional wisdom and engage in trial and error collaboration with industry makes such breakthroughs possible.

The Gleevec story shows that medicine, like all successful human endeavors, is driven by equal parts knowledge, ambition and, yes, luck. Medical innovation is often a humbling process, but the Lasker Award reminds us that we should not make it any more difficult through unnecessary regulations.

Note:
Thomas Stossel is a professor of medicine at Harvard and a fellow at the Manhattan Institute.