I Message from the Institute Directors

Cancer is now understood to include more than 200 different diseases. In all forms of cancer, genomic changes — often specific to a particular type or stage of cancer — cause disruptions within cellular pathways that result in uncontrolled cell growth.

A more systematic understanding of cancer genetics could provide important insights into the molecular pathways that, when disrupted, lead to the uncontrolled growth of cancer cells and enable their spread throughout the body. This genetic information could provide powerful advances in cancer clinical research and disease management. It could lead to an expanded catalog of new therapeutic targets, as well as new ways to categorize tumors that would allow clinical trials to focus on those patients who are most likely to respond to specific treatments.

Thanks to the tools and technologies developed by the Human Genome Project and advances in using genetic information to improve cancer diagnosis and treatment, we can now envision a systematic, comprehensive effort to map the changes in the human genetic blueprint that are associated with cancer.

Genetic mutations linked to breast cancer, colon cancer, melanoma, and other cancers already have led to diagnostic tests that can point to the most effective intervention. Recent discoveries in cancer genomics have helped to identify several treatments that work by targeting cancer cells with a specific genetic change, such as Gleevec®, a drug for chronic myeloid leukemia and gastrointestinal stromal tumors, and Herceptin®, a drug for one form of breast cancer. These successful developments support further examination of the molecular origins of cancer to more quickly develop new tools to diagnose, treat, and prevent cancer.

The application of genomics to cancer research could not come at a more opportune time given the recent exponential increase in our understanding of the process of how cancer develops. To ensure that we capitalize on this opportunity to make dramatic progress, NCI and NHGRI have developed The Cancer Genome Atlas (TCGA) — a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing. The overarching goal of TCGA is to improve our ability to diagnose, treat, and prevent cancer.

Over the past year, NCI and NHGRI have held numerous meetings exploring the potential for this joint project. In July 2005, NCI and NHGRI convened a workshop in Washington, D.C. entitled “Toward a Comprehensive Genomic Analysis of Cancer.” This workshop brought together basic researchers, clinical researchers, health care professionals, bioethicists, cancer survivors, and other members of the U.S. and international cancer and genomic communities to assist in outlining the most effective strategies for the development of a successful effort to better understand cancer genomics.

The goal of TCGA is to develop a comprehensive catalog, or atlas, of the many genetic changes that occur in cancers, from chromosome rearrangements to DNA mutations to epigenetic changes — the chemical modifications of DNA that can turn genes on or off without altering the DNA sequence. TCGA will swiftly place all of the data it develops into free public databases for use by the broader cancer research community.

Embarking on such an ambitious venture requires significant planning. NCI and NHGRI are taking a phased approach to ensure that the appropriate technologies, systems, and processes will be developed and evaluated in the context of a high-throughput effort. The first phase is the TCGA Pilot Project, which has clear milestones and goals that must be met before a large-scale effort is initiated.

NCI and NHGRI have each committed $50 million over three years to the pilot project to develop and test the complex science and technology framework needed to systematically identify and characterize the genetic mutations and other genomic changes associated with cancer. In so doing, the pilot project will assess the feasibility of a full-scale effort to systematically explore the entire spectrum of genomic changes involved in human cancer.

The potential of a cancer genome “atlas” is tremendous, enabling detection of disease early when it is curable, distinguishing responder from non-responders to therapy, providing new targets for drug development, and, ultimately, providing prevention strategies for people at risk for developing cancer.

Finally, this is not just a project of NCI and NHGRI, but a call to action for the clinical oncology and research communities. TCGA has been and will continue to be a team effort. Along the planning pathway, we received a tremendous amount of input and support from cancer survivors, clinicians, and researchers about this undertaking. This collaborative spirit, in our view, is a prologue to the achievements that we foresee from TCGA. By joining together, we are confident that we will continue to make substantial scientific and medical progress to achieve the goal that matters most: eliminating suffering and death due to cancer.

Francis S. Collins, M.D., Ph.D.
Director
National Human Genome Research Institute

Andrew C. von Eschenbach, M.D.
Director
National Cancer Institute

December 2005