Director's Update: December 2, 2003
When I entered the field of oncology thirty years ago, the revolution in molecular biology and genetics was only beginning - and with it, an exciting new era in molecular oncology. At the time, the cancer cell was, for the most part, a "black box" to us, and as a result, we had little understanding of how cancer develops and progresses to a life-threatening disease. Today, because of this biomedical revolution, our knowledge of cancer development has evolved dramatically. We have documented many of the genetic alterations in the cancer cell that underlie cancer development and have characterized how these alterations disrupt the proper functioning of selected pathways inside the cell. This more robust understanding of the molecular underpinnings of cancer has changed the course of cancer research and - as I have witnessed first hand in the clinic - has fueled new approaches to prevention, detection, diagnosis, and treatment. Yet, this research also has revealed that the cancer cell is only part of the story in cancer development. Mounting evidence now suggests that a cancer cell interacts with its local and systemic microenvironments, and each profoundly influences the behavior of the other. These tumor-host interactions permit, and even encourage, cancer progression.
Two years ago, the National Cancer Institute identified the tumor microenvironment as a priority research area in an effort to expand our knowledge of the cells and factors that normally populate the microenvironment as well as to advance our understanding of how these microenvironment components interact with tumor cells. To identify the most promising avenues of research in this growing area, we convened the first of a series of scientific workshops involving leading scientists and asked them to help us identify key questions and research approaches to consider as we crafted our long-range strategic plan. Based on these discussions, we have developed and funded several initiatives over the past year, including studies using imaging technology to study the molecular and cellular underpinnings of tumor-host interactions; investigations to develop and apply organotypic models to study tumor-host interactions; and - in collaboration with the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Arthritis and Musculoskeletal and Skin Diseases - studies exploring the molecular interactions between tumor cells and bones. We have also recently announced a number of new initiatives, several of which we are undertaking in partnership with other institutes of the National Institutes of Health. For example, we are working with the National Institute on Aging to advance our knowledge of age-related changes in tissues. We hope that studies from this initiative will improve our understanding of age-associated changes in the cellular microenvironment and clarify why the aging microenvironment may be more supportive of tumor growth. We are also partnering with the National Heart, Lung, and Blood Institute to encourage research on the biology of the lymphatic system and mechanisms underlying the development of lymphedema. Through studies supported by this initiative, we hope to better understand how the lymphatic system allows solid tumors to metastasize to distant organs in the body.
Last month, we again called together experts in this area through our Think Tank series. We asked these scientists to consider if the questions we identified two years ago are still valid and if the approaches we have undertaken to answer these questions are still the most promising. Through two days of fruitful discussions, the Think Tank participants helped us to take stock of our progress to date and concluded that our current efforts are taking the field in the right direction. But, recognizing the need to build on this progress, they identified select research issues and needs that, if pursued in the near term, will rapidly advance the science in this area. For example, they noted the need for the development of in vitro and in vivo models that more accurately reflect the physiologic and pathologic situations in human malignancy. They encouraged further studies of the normal tissue environment as a prerequisite to understanding the tumor microenvironment and noted that such studies would benefit enormously from the creation of a repository containing stromal cells and matrix molecules from normal and malignant tissues. They identified the need for the development of model systems that can be used to discover and validate therapeutic targets within the tumor microenvironment and the importance of moving mouse and human research forward simultaneously to help us discover useful targets. And, they acknowledged the need for a systems approach to the study of the tumor microenvironment to enable us to better understand the complex systems of cancers networks within cancer cells, as well as between cancer cells and their environment, so that we may discover new leads for cancer prevention, detection, diagnosis, and treatment. NCI is now considering how we might best address these needs. These recommendations will help to guide our ongoing and future research efforts.
I am excited about the prospects we now have for scientific advancement in this important area. Greater knowledge of the tumor-host relationship will considerably improve our efforts to effectively prevent, detect, and treat cancer, and will bring us ever closer to the day when people can live with - and not die from - this disease.
Andrew C. von Eschenbach, M.D.
Director, National Cancer Institute
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