© 2000 by Oxford University Press
Journal of the National Cancer Institute Monographs, No. 27, 13-14,
2000
© 2000 Oxford University Press
Introductory Remarks
Affiliation of author: Division of Cancer Biology, National Cancer Institute, Bethesda, MD.
Correspondence to: David G. Longfellow, Ph.D., National Institutes of Health, 6006 Executive Blvd., Suite 220, MSC 7055, Bethesda, MD 20892-7055 (e-mail: dl585{at}nih.gov).
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INTRODUCTION |
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 TopNotes Introduction |
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The International Symposium was sponsored by the Division of Cancer Biology (DCB) of the National Cancer Institute (NCI). The organizers of the symposium are also pleased to acknowledge the generous support of the National Institutes of Health Office of Research on Women's Health and the Susan G. Komen Breast Cancer Foundation. Special gratitude is expressed for the invaluable assistance of Karen R. Grotzinger, NCI, for meeting coordination. The organizers also thank Mrs. Fran Oscar and her staff at Palladian Partners for their excellent logistical and on-site support. The preparation of this monograph would not have been possible without the dedicated effort of the monograph editors, Drs. Ercole L. Cavalieri and Eleanor G. Rogan, of the Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, together with the expert technical assistance of Mr. Harry W. Bullerdiek.
The March Symposium was the intellectual outcome of a new NCI extramural initiative, a focus group on estrogen carcinogenesis. This focus group is known as the "Cancer Cube." The term "Cube" is derived from the essential elements on which this focus group is based: Complementary, Collaborative, Coalition, which is "C" to the third power (C3). The "Cancer Cube" that is currently being piloted by the Chemical and Physical Carcinogenesis Branch in the Division of Cancer Biology is a new paradigm for NCI to facilitate cancer research. The Cube is composed of active researchers who have, by mutual agreement, joined forces in an ongoing effort to better focus on a scientific question or problem in cancer that is of interest to the NCI and the National Cancer Program. The goal that this group has established for themselves is to achieve synergism in the overall effort by enhancing the individual research of the members through scientific collaborations and sharing of resources, techniques, and data.
Cancer Cubes can be thought of as "building blocks" to new understanding. The driving force behind the development of this initiative was NCI's desire to find innovative approaches to facilitate progress, the recognition that a critical mass of collaborating scientists is sometimes needed to achieve momentum, and the recognition in this first Cube activity that maverick viewpoints were beginning to converge and complement each other. A frequent recommendation from workshops in various areas of cancer research is that multidisciplinary expertise is needed to address the unanswered questions. However, funding mechanisms typically used to address such needs are cost-intensive and face considerable obstacles in review to overcome the initial inertia of formation. Once funded, these grants must compete with other large-dollar initiatives to maintain continuity.
The C3, on the other hand, is not a funding mechanism. It recognizes that active investigators are usually on "soft" money and, as a matter of course, will obtain research project grants to pursue their scientific interests. The vast majority do this through the R01 mechanism. The C3 seeks to allow scientific interests and not the funding mechanism (e.g., P01, P30, or U01) to drive the collaborative process. The only initial expense is in bringing the interested parties together to explore their interest in collaborating and then meeting on a regular basis (such as twice a year) to review progress and design new initiatives. With time, it is recognized that the activities of a Cube will increase the demand on core resources as the utilization of reagents, animals, and the like expands. This need can initially be addressed through administrative supplements. Eventually, it is envisioned that a shared resource mechanism (e.g., an R24) could serve to provide free-standing cores for the collaborative efforts of the Cube.
The size of a Cube is not artificially limited by budget constraints but by human dynamics of interaction. The limitation in participants is regulated more by practical issues of discussion and interaction. This number is probably on the order of less than 20 participants. All members are participants in the intellectual process and sharing, but there is no need to collaborate with all of the players at the same time. This distinguishes a Cube from the dynamics of a program project grant (P01) where there would typically be five to six investigators engaged around a central topic. A group of 18–20 researchers provides a richness of diversity in discipline and training and more important, in a viewpoint that one doesn't usually find in the existing funding mechanisms. Highly desired multi-institutional collaborations are easily facilitated, in effect creating an "institute without walls."
Measures of success for an initiative like the C3 will perhaps vary with the goals set, but some quantifiable measures might include evidence of the following: collaborative publications, new collaborative projects, generation of new concepts, movement of the field forward, new insights into the mechanisms of cancer, translational progress from experimental design to clinical application, and prevention/intervention strategies.
The concept for the first C3 was developed by an NCI scientific program director, Dr. David Longfellow, who contacted two investigators who were already collaborating and who were committed to making progress in the field of estrogen carcinogenesis. The remaining potential participants were identified and contacted initially by those two investigators. A major consideration was to identify investigators who would bring to the group the range of needed expertise. This Cube began with a roster of 17 members and has since added a member from the breast cancer advocacy community. In its early meeting, the C3 selected three co-chairs and a central question was developed as a focus and a reachable goal for the group's endeavors. The C3 decided to meet twice a year to reassess and fine-tune their research.
The research question that the C3 chose to address was: Do estrogenic compounds induce genotoxic events leading to cancer? Their specific focus is to raise the awareness and understanding of nonreceptor-mediated modes of action. They hypothesize that estrogen tumorigenesis requires the metabolic activation of estrogens to reactive intermediates. Tumors would develop from cells genetically damaged by specific estrogen metabolites and proliferating in response to estrogen receptor-mediated stimuli.
By the fourth meeting of the C3, plans were consolidated to develop a major international symposium. It was envisioned that this meeting would set the stage to develop a more holistic understanding of the role of estrogens in carcinogenesis both through traditional aspects of estrogen receptor binding but also through nonreceptor-mediated mechanisms. World experts were invited to participate. Topics included metabolic activation of estrogens to carcinogenic forms, deactivation of carcinogenic metabolites, and the role of estrogen receptor-mediated processes in tumor induction. One of the goals of the symposium was to provide attendees with an overview of the direction of research on estrogen-induced cancer. Another goal was to identify biomarkers that can be useful in studies of cancer risk among humans and in the future development of preventive strategies. The symposium was very well received by an audience of approximately 160 participants. The 2-day meeting concluded with a panel perspective from the advocacy community with the major organizations in breast and prostate cancers. A preview of the actual meeting, which appeared in the March 13, 1998, issue of Science, entitled "New role of estrogen in cancer?", was based on extensive background interviews with a number of the major speakers.
This monograph seeks to tell the story of estrogen research to date and can serve as a resource for both the scientific and lay communities. It will also serve as a record of the scientific progress to date of the Cancer Cube Focus Group on Estrogen Carcinogenesis.
In summary, the first C3 has demonstrated the success of this approach to stimulating new understandings in estrogen carcinogenesis in particular but indeed for cancer etiology and prevention in general. C3 members are publishing together; submitting joint grant applications; visiting and lecturing at each other's institutions; establishing resource, technology, and tissue networks; and strengthening the body of literature in this area of research through their complementary efforts.
To provide opportunities for other researchers to experience similar collaborative success, NCI has made available $1.125 million per year to the DCB to promote similar collaborative research efforts. In response, the DCB has announced a new initiative entitled Activities to Promote Research Collaborations (APRC), the purpose of which is to promote and facilitate research collaborations in basic cancer research. Limited supplemental support is available for meetings or workshops and for grant-related research activities (e.g., consortia) to establish focused scientific research collaborations in novel and promising areas. To date, four rounds of submission and review have occurred (two in FY98 and two in FY99), resulting in 17 consortia APRC awards totaling $1.574 million and six workshop APRC awards totaling $134 000. Three subgroups of the C3 have successfully competed for consortia awards under this initiative.
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NOTES |
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Editor's note: This monograph is based on an International Symposium on "Estrogens as Endogenous Carcinogens in the Breast and Prostate," which was held at the Westfields Conference Center in Chantilly, VA, on March 16 and 17, 1998. It is not in the strictest sense a "proceedings" of that symposium, but the editors of this monograph have sought to enhance the presented materials and to integrate them into a text that will enable greater readability. To that end, the chairpersons of each of the sessions of the symposium have also served as editors of their respective sessions to integrate the contributed manuscripts into chapters for this monograph.
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