Point of View

Rules should allow cancer researchers to be bold

May 23, 2014 


Cancer cells

WILDPIXEL — Getty Images/iStockphoto

The medical team was on morning rounds, outside the room of one of our patients, Ellie. She was smart, articulate and dying from metastatic cancer. It would be easy to use clichés to describe her, but she was more than a series of words. Ellie was vibrant and lived in the moment.

So it was not surprising that morning when she confronted 60 years of cancer research. Our attending physician shared the daily plan and asked his customary transition-out-of-the-room, “Do you have any questions today?” She sat silent, deliberately increasing the tension in the room. Finally, she spoke: “Do you believe in chemo?”

A century ago, no one believed in chemotherapy. The only approach to cancer was surgery. However, some cancers, such as leukemias, are in the blood, making surgical cures impossible. Famed pathologist Sidney Farber discovered that certain chemicals could halt these cancers of the blood. Farber’s chemically based medicines were not just a new treatment, but a new way of thinking about treating cancer, launching a war that has been waged since.

Paradigms established by researchers such as Farber have improved treatments, but our success at eradicating cancers in preclinical models of mice and cells has not borne out in patients. Only 5 percent of anti-cancer compounds identified in the preclinical setting make it past Food and Drug Administration approval, and fewer still substantially prolong survival. After adjusting for age and size of the population, from 1950 to 2005, cancer death rates have dropped only 5 percent. During this same period, the death rate for cardiovascular diseases has dropped 64 percent. More worrisome, financial support for future research from the National Institutes of Health is at a historic low.

Like Farber, we see the current state of cancer research and wonder: How can we do better?

For one, we could learn from Silicon Valley. Young investigators, including graduate students and post-doctoral researchers, should be encouraged with strong mentorships and sustainable funding options to explore new preclinical models that emphasize how surrounding nontumor cells that naturally inhabit our bodies impact a growing tumor. Universities and grant funding organizations should provide alternatives to traditional lab hierarchy and cultivate collaborative startups among young investigators. This will inevitably lead to failures, but without permitting risk we punish those who seek disruptive advances.

Another reason for our risk aversion is how human clinical trials are conducted. The last and most important step for developing FDA-approved drugs is a costly phase III trial. Whether a drug prolongs life by eight weeks or eight months, the monetary rewards are likely to be similar. Therefore, we are too quick to say “this drug is good” and too slow to say “this drug is not good enough.” We should shift resources away from phase III clinical trials toward more early-stage trials that find treatments with lasting results.

In addition to finding new cancer treatments, we should invest in cancer prevention. Curbing smoking and developing vaccines for hepatitis and human papilloma viruses have been estimated to reduce new cases of lung, liver and cervical cancer by more than two-thirds. Clinical trials have shown that tamoxifen, used in treating breast cancer, can also prevent the disease in some high-risk patients. Just as cardiologists have invested in proving the efficacy of statins in preventing heart attacks, we should develop studies to prevent cancer.

Many patients are alive today because of chemotherapy. But patients like Ellie cannot believe in chemotherapy because today’s chemotherapy has failed them. The work of many dedicated scientists has resulted in tremendous gains in cancer treatment, but we cannot be bound by the current way of doing things. We must try to seek new ideas, fail and try again. That requires boldness – not just from us, but from everyone who is fighting this terrible war on cancer.

Isaac S. Chan, Ph.D., recently received his M.D. at the University of North Carolina at Chapel Hill. William R. Jeck, Ph.D., is a medical student there.

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