Despite many decades of investigation and progress that's been made in early diagnosis and treatment, the exact causes of most cancers remain unknown. For most of the cancers we treat, there exists a heterogeneous mix of genetic changes and numerous potential environmental influences that challenge the development of simple prevention strategies.

This has resulted in a level of frustration by the public regarding the primary prevention of cancer, including scientifically based recommendations for diet and lifestyle interventions. In recent years this public frustration has included the development and testing of targeted preventive oral agents that have often carried significant risk of causing a shift to other diseases or compromising daily quality of life. Our patients have clearly told us they are unwilling to trade healthy lives for these risks, even in the face of a risk of cancer.

As was discussed in detail in a recent special issue of the NCI Cancer Bulletin, we are beginning to view our approach to prevention research differently, and it's an approach that NCI hopes will lead to more dramatic advances. This approach is defined by the use of advanced tools and technologies - such as those employed in genomics, proteomics, and metabolomics - to pursue the molecular events associated with the mechanisms and early signs of cancer development.

Cancer prevention is complex. It will require our understanding of germline abnormalities, compounded by somatic mutations throughout our lifetime, defined by protein expression patterns and cellular function. These events will be further impacted by the need to understand pharmaco-genomics, environmental exposures, and lifestyle factors. All of these layers point to the difficulty of finding effective, nontoxic preventive agents.

Part of the solution involves identifying biomarkers of risk, such as ongoing efforts to identify epigenetic changes like hypermethylation that are linked to cancer risk, as well as genome-wide association studies, such as the recent studies, including those led by NCI's CGEMS program, that identified new genetic variants significantly associated with breast and prostate cancer risk.

Prevention also is about detecting disease in its earliest stages, and NCI's Early Detection Research Network is supporting researchers who are making important inroads in this area, including, for example, promising preliminary work on an early detection assay for pancreatic cancer.

NCI's cancer prevention research program has generated some remarkable success stories, including the dramatic drop in smoking rates over the past two decades, as well as the approval of tamoxifen as the first and still only drug approved by the FDA for the prevention of breast cancer.

And even as our interest in molecular prevention grows, we continue to support research into lifestyle and environmental factors that influence cancer risk. That includes anti-obesity programs aimed at minorities conducted under the auspices of the Transdisciplinary Research on Energetics in Cancer program, as well as the development of new chemopreventive agents, including a novel class of chemopreventive agents called triterpenoids being led by Dr. Michael Sporn and colleagues at Dartmouth University.

Clearly what is being presented here represents a new paradigm for cancer prevention. It will also ensure that we can achieve the greatest risk reduction at the lowest possible safety risk, something that must and will always be our guiding principle.

Prevention is and will continue to be an integral part of reducing cancer's burden, and it's something to which NCI is deeply committed.

Dr. John E. Niederhuber
Director, National Cancer Institute