Basic Science Leads the Charge in the War on Cancer
In an article in a recent edition of Fortune magazine, Clifton Leaf, a cancer survivor, assesses the state of the war on cancer and concludes that we are losing. Moreover, he proposes a game plan for winning it. Is he right? In many ways, yes, he is right. He argues that we should focus on cancer as a process and fight it at its earliest stages when it is highly curable rather than at later stages where battle after battle has failed. He argues that drugs should be tested on patients earlier in the cancer process rather than on patients who have failed to respond to all other treatments, as is currently done. He argues that cancer, like AIDS, will require multiple drugs and that we need to test multiple drugs in combination, some of which may have no efficacy in isolation. While I agree with each of these recommendations, he fails to note that they are only now becoming possible and that these new opportunities derive from the very source he denigrates: fundamental knowledge provided by basic science.
Consider each of his points above in turn. There is currently no technology able to examine comprehensively all of the molecules in the blood for early diagnosis of disease. This means that it will be necessary to focus molecular diagnosis on molecules known to be abundant in tumors or involved in tumor processes. This knowledge is coming from basic research in cancer. It may well be productive to test new drugs in patients with earlier stages of cancer and to test new drugs in combinations, although both approaches would face ethical and regulatory hurdles. If either can be accomplished, that would not be done without excellent information suggesting potential efficacy. That information would come from drug target validation in human cells, a technology dependent on small RNA molecules, only discovered in the last couple of years as a result of basic research. It is definitely too soon to throw out basic science!
NCI Director Andrew C. von Eschenbach has called for the cancer community to eliminate the suffering and death from cancer by the year 2015. Given the poor state of progress toward it to date, one must ask: Is this possible? What is important about this challenge is not the precise date but the sense of urgency, the same sense of urgency expressed by Mr. Leaf. As a cancer center director, I have experienced the sense of urgency of our patients, donors, and board members. People who support cancer research and experience cancer in their families expect us to focus on eliminating this disease now. I think they are all correct in thinking that a more effective approach is possible and should be applied post haste. I believe the answer is in methods to detect cancer earlier and monitor the effectiveness of drug interventions quickly and individually. We know that early detection of disease cures cancer by surgery alone for cervical, colon, and esophageal cancer.
Implementing this new approach relies on exploiting recent technology and knowledge in the area of molecuBasic Science Leads the Charge in the War on Cancerlar diagnostics. The completion of the human genome project provides us a guide to all potential protein molecules in our blood. Recent advances in the technology of mass spectrometry allow for an unprecedented analysis of those proteins. Knowing the proteins associated with cancers will allow us to exploit recent advances in molecularly targeted imaging to locate very small tumors and interrogate their molecular features. Drugs attached to agents that seek out the proteins on cancer cells can deliver therapy directly where it is needed. I believe this is what the winning battle with cancer will look like.
Mr. Leaf calls for a coordinated assault on this disease, an approach also championed by Dr. von Eschenbach. Why a coordinated assault? We learned from the human genome project that achieving some goals in biology requires the type of coordination that is common in physics and engineering but rare in biology and medicine. This is one of those goals. Many players in the cancer community are needed to implement a major direction change from a focus on drugs for late-stage disease to one using effective diagnostics at earlier stages for detection and treatment. A paradigm shift cannot be effective if it does not engage the entire community. With NCI leading a coordinated effort involving the research community, the Food and Drug Administration, pharmaceutical and biotechnology industries, and advocacy groups, we can win the war on cancer.
Dr. Leland Hartwell is President & Director of the Fred Hutchinson Cancer Research Center