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Seven Ways to Challenge Cancer


Nearly four decades after US President Richard Nixon declared war on cancer, scientists and clinicians alike are still largely stymied by this multitude of related diseases. To be sure, our understanding of cancer, treatments for it, and patient prognosis at detection have all improved markedly. Once-deadly prostate cancer is for many men now an inconvenience, and the number of breast cancer survivors grows annually. But certain types of cancer — pancreatic, lung, or liver, to name a few — remain a virtual death sentence. With more than 220 recognized types of cancer out there, the complexity factor alone is formidable.

In the face of this, it's all too easy to pass the blame around as to why we still haven't found a cure for cancer. Easy targets include pharmaceutical companies, regulatory agencies like the US Food and Drug Administration, and even researchers. But passing the blame buck doesn't help patients. In honor of our annual cancer special issue, Genome Technology tracked down some of the leading experts in the field to find out what steps can be taken now to have the most immediate impact on speeding up the march of promising research to widespread effect in the clinic.

The goal here isn't to suggest that large-scale biology hasn't led to progress in cancer. NIH Director Elias Zerhouni points to the lung cancer drug Iressa as one example of such an advance: "Now with genomic technologies," he says, "you can identify patients that will respond to the medicine versus patients that will not respond." He adds that as time goes on, it will become even more evident that today's innovations will have a major effect on patient care.

The purpose of this article is to focus on practical changes that can be made today to have a real and noticeable change in the lives of cancer victims. To that end, here are the seven steps our experts say could have the biggest impact in the battle against cancer right now. 

1. Promote multidisciplinary teams throughout the process, but particularly in early research.

Genomics, proteomics, and related sciences have led to a solid characterization of biomarkers linked to cancer, says Zerhouni, but there's still a gap in our knowledge of how cancer functions overall. He says that early stages of research will get the boost they need to accomplish this if people from different backgrounds team up to tackle it. "We need to have a multi-targeted approach to cancer, and a rational one," he says. He believes basic researchers need to work more closely with translational scientists. "You need interdisciplinary approaches from the get-go," he adds, pointing to the Cancer Genome Atlas as one example of a well-conceived model where basic meets translational research.

2. Focus on understanding the biology of cancer, rather than just making drugs to treat the symptoms.

Pharmas are in the business of coming up with treatments for illnesses — not necessarily elucidating the biology behind how a disease functions. Richard Pazdur, head of the Office of Oncology Drug Products at the FDA, says there needs to be more effort in the scientific due diligence of cancer. "What I'm talking about is really a thorough understanding of a disease. … This really needs to be more of a focus, to have a better understanding of the molecular basis of disease," he says. "Once we do that, it's going to be much easier." While pharmas and biotechs can make strides here, it's really an opportunity for academic researchers to home in on cancer biology and educate the community as a whole.

3. Enroll more patients in clinical trials.

Experts lament the shortage of patients who opt to enroll in clinical trials — and with hundreds of cancer drugs in development, the need for such people is only growing. Part of the problem is a necessary evil: patients know that their chance of being given a potentially life-saving experimental drug is tempered by the chance of being given nothing more than the standard level of treatment. According to H. Kim Lyerly, director of the Duke Comprehensive Cancer Center, "Only three percent of adults with cancer enroll in clinical trials, yet through these trials they can receive the most innovative drugs available in the world."

Robert Bast, VP of translational research at the MD Anderson Cancer Center, says that one way to make progress in this field is to deal with the reimbursement side. "There's not consistent and uniform reimbursement of patient care costs for patients who are on trials," he says.

4. Consistently deliver funding for translational research.

The NIH budget crunch is no secret, and while NCI's portion of that is generous, the flat budget has meant that "we're probably down 16 or 20 percent from five years ago" thanks to inflation, Bast says. He contends that the lack of consistent funding is a major challenge in the cancer arena. "It's always been tough to get money for translational research," he adds. 

5. Improve communication between regulatory agencies, drug development companies, and academic institutions.

Zerhouni says that getting more people on the same page would be a big win for the cancer community. "The cancer centers and all the connections they have with industry have worked," he says, noting that extending those kinds of interactions would be a boon to the field.

As Duke's Lyerly puts it, "We need continued dialogue throughout the drug development process that allows more open and collaborative discussions about a drug's viability." His center co-hosts an annual workshop to "bring together leaders in clinical and translational cancer research [to] expedite the development and validation processes for new anticancer and cancer prevention agents so they can be made available to patients at an accelerated rate."

6. Broker partnerships among pharmaceutical companies for multiple-drug clinical trials.

Clinical trials generally test one therapeutic, but in the real world, cancer patients are almost always prescribed cocktails of multiple drugs. Bast says one challenge is performing clinical trials with many drugs because that generally means getting pharmas to work with each other. "It would be very helpful to have more collaborations across companies," he says.

7. Keep drugs that perform marginally off the regulatory agencies' to-do list.

FDA's Pazdur doesn't mince words about the problem as far as his agency is concerned, and that's drug companies that submit sub-optimal candidates for approval. "We have to expend a large amount of resources by sorting through drugs that should have never been filed," he says. "For many of the small companies, if you only have one drug, it can be a life-saving event to put forward a drug to the FDA, even if the clinical trial is dubious or failed."

Because of that, Pazdur believes the FDA is indeed a bottleneck in the race to cure cancer — but it's a bottleneck because it's clogged with submissions that have to be weeded out. "The problem is in drugs that are marginal," he says. "We all understand the problems in treating oncology patients, but we're not benefiting anyone to put on the market a drug that doesn't work or has a really unfavorable risk-benefit ratio." 

Standing in the Way

Genome Technology Online ran a poll to find out what readers feel is the main holdup to getting promising research to the clinic. Here's what you said:

What's the biggest barrier between great cancer research and broad clinical impact?

32%  Time
The advances are on the way, but it just takes a long time for drug development and clinical trials.

28%  Science/technology
We're still waiting for a big breakthrough.

21%  Funding
Scientists at universities and in industry need more money for the work.

10%  IP
Too much is locked up in patent portfolios, preventing significant progress.

9%  Regulatory agencies
FDA and its counterparts need to be more proactive and efficient. 

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