Q&A: Powel Brown on Cancer Prevention Research

Cutting-edge studies are suggesting ways to thwart cancer development and recurrence

These days, cancer prevention research goes far beyond studying, for example, what makes smoking cessation efforts successful. “It spans all phases of scientific endeavor, from the most basic laboratory work all the way to clinical and epidemiologic research,” explains Powel Brown, MD, PhD, chairman of the Department of Clinical Cancer Prevention at The University of Texas MD Anderson Cancer Center in Houston. “It's also critical work.” Brown spoke with Cancer Discovery's Suzanne Rose about how prevention research might ease the growing burden of cancer.

What types of studies are being done across the spectrum of prevention research?

In basic science, we try to understand the process of carcinogenesis—discovering driver oncogenes and describing ways to target them to arrest cancer development. In preclinical studies, scientists use animal models to help identify effective cancer-preventive drugs, as well as to test vaccines and immune-based strategies. The most promising interventions are being tested in clinical trials to see if they can prevent primary cancers or second cancers in people with a prior cancer. Population studies help identify groups of people who may have a higher risk for certain cancers. A major advance is the use of risk-based preventive interventions, or tiered intervention, in which preventive approaches are tailored to a person's risk of developing cancer.

What's an example of risk-based prevention intervention?

Women at normal to moderate risk of breast cancer may benefit from behavioral modifications, such as increased exercise, while women at high risk might benefit from taking medications, such as tamoxifen or raloxifene. Women at extremely high risk may opt for prophylactic surgery. This approach is patterned after heart disease prevention efforts, in which cholesterol measurements can tell us which patients need to take cholesterol-lowering drugs. Unfortunately, we don't have a modifiable marker like cholesterol to identify individuals at risk of cancer and to follow to see if an intervention is effective. Until we have something like that, the concept of preventive therapy with medications may not be fully embraced.

Is that why more people haven't gotten the human papilloma virus (HPV) vaccine?

There have been concerns about widely offering the HPV vaccine, which could greatly reduce the incidence of cervical cancer, to young teens. However, the uptake of the HPV vaccine has been vastly superior to the uptake of tamoxifen for breast cancer prevention or finasteride for prostate cancer prevention. Although these drugs have side effects that have limited their use, they have been shown to reduce the incidence of cancer. In my opinion, they aren't used often enough. We need to get the message out that, for certain people, the benefits of these medications greatly outweigh the risks.

Your research focuses on breast cancer prevention. What's happening there?

We and others have been working on targeting the HER2 protein to prevent HER2-positive breast cancer. Human clinical trials have shown that we can effectively treat HER2 breast cancer with anti-HER2 drugs, and an anti-HER2 vaccine is showing promising results. The next step is to see if these approaches can prevent HER2-positive cancer.

Cutting-edge research is also under way to determine the most effective way to treat and prevent triple-negative breast cancer, which is driven by p53 mutations. The mutant p53 protein has been particularly difficult to target; however, new drugs that revert mutant p53 to a wild-type conformation show great promise in both therapeutic and preventive settings. We and others have identified drugs that target critical kinases activated in p53 mutant cells. Inhibitors of these kinases, if given early in tumorigenesis, may effectively prevent p53 mutant cancers.

What prevention research would you like to see?

Studies suggest that aspirin users have a decreased incidence of cancers, so there's interest in using it for prevention. We need to assess its preventive effects in large phase III trials.

Recent studies show that increased inflammation promotes cancer, and thus drugs that block inflammation may prevent cancer. Because some anti-inflammatory drugs, such as COX-2 inhibitors, have significant rare toxicities, we need to find the best way to target inflammatory pathways.

I would also like to see clinical trials testing pharmaceutical agents in combination with either dietary or exercise interventions to more effectively prevent cancer. For example, epidemiologic data suggest that the diabetes drug metformin might be cancer preventive, especially with a healthy diet and/or increased exercise.

Are drug companies addressing cancer prevention?

Many compounds have been shown to prevent cancer in preclinical models, but few companies want to develop them. I think that's because of concerns about rare toxicities, which present a liability for the drug company. Such toxicities can cause a drug to be pulled from the market, as was the case with the COX-2 inhibitor Vioxx. Pharmaceutical companies watched that carefully and have become less interested in developing drugs for prevention. Concern over rare toxicities has greatly slowed progress in this field.

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