Cancer Chemoprevention

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Craig Elmets, M.D.
– Co-Leader

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Clinton Grubbs, Ph.D.
– Co-Leader

Overview:

The goal of the UAB Comprehensive Cancer Center Chemoprevention Program (CCP) is to prevent cancer through pharmacological intervention or nutritional manipulation (through functional foods and supplements).  The program is interdisciplinary and translational in nature.

The CCP program was established as a distinct entity within the UAB CCC as the development of chemopreventive agents differs substantially from development of most other therapeutic modalities. Chemopreventive agents must be administered on a long-term basis to healthy individuals; hence, emphasis must be placed not only on efficacy but also on a high level of safety.  In addition, cancers develop through a multistep process in which molecular and biochemical alterations accumulate in target cells over long periods of time, the end result of which is a clinically apparent malignancy.  Development of effective chemopreventive agents, or combinations of agents requires identification of the points in this process in which intervention with a pharmacologic agent or changes in diet through consumption of natural botanicals or modification of diet-related components could inhibit, reverse and/or delay development of invasive and/or metastatic cancers and a knowledge of their mechanisms of action. As the CCP was established as a pilot program in 1999 and achieved full program status in 2002, the Program has accumulated the critical mass of experts in the field necessary to sustain innovative research as well as establishing critical ties with NCI initiatives in this field, the Consortium for Early Phase Human Chemoprevention Trials, and industry.

The 18 members of the CCC CCP are drawn from 10 departments and 5 schools. They are active in identifying novel chemopreventive agents capable of preventing cancer; conducting basic laboratory studies on the ability of naturally occurring and synthetic chemicals to prevent or delay the process of carcinogenesis, and then determining their mechanisms of action; developing and characterizing model systems useful in the evaluation of potential chemopreventive modalities; performing early phase chemoprevention trials evaluating novel chemopreventive agents; and identifying biomarkers or other characteristics that will predict the response to chemopreventive agents in patients.  These members have 206 publications, 35% intra-programmatic, 28% inter-programmatic, and 34% inter-institutional.

The Program has a well-established focus on synthetic retinoids, nonsteroidal anti-inflammatory drugs (cyclooxygenase inhibitors), and phytochemicals.  In the current funding period, the program has taken steps to incorporate the recent advances in identification of biomarkers of risk into the development of chemoprevention strategies.  In parallel, the program has committed resources to the development of models that are needed for progress in the field of evaluation of the efficacy of chemopreventive agents. The scope of the program and the depth of expertise have been expanded by strategic recruitment and a mentoring program.  Innovative, transdisciplinary research is nurtured through focused working groups and hands-on workshops.

The scientific aims of the program are to:

1. Conduct basic and clinical studies to evaluate potential synthetic chemopreventive agents:

  • UAB30 and other RXR retinoids (rexinoids) designed and synthesized at UAB (prevention of breast and non-melanoma skin cancer);
  • Modulators of immune and inflammatory responses in the prevention of epithelial malignancies (prevention of skin, bladder and breast cancer).

2. Identify and exploit the molecular and biochemical properties of phytochemicals and dietary components (prevention of breast, melanoma, lung and colon cancers).

  • Polyphenols: Flavones/flavonoids, Pro-anthocyanidins, and Anthocyanidins
  • Micro-nutrients: Folate (prevention of cervical cancer); vitamin D

3. Utilize modeling systems to assist in the identification and development of new chemopreventive strategies:

  • Identify prime targets in carcinogenic pathways;
  • Develop needed pre-clinical animal models;
  • Integrate molecular biomarkers of risk in clinical evaluation of chemopreventive agents.

Click here for a complete list of Cancer Chemoprevention Program Members

Leadership:

Craig Elmets, M.D., a Senior Scientist in the UAB Comprehensive Cancer Center, serves as one of the Directors of the Cancer Chemoprevention Program. He is Professor and Chair of the UAB Department of Dermatology, a position he has held since 1997. He is also Director of the NIH-funded UAB Skin Diseases Research Center and the UAB T32 Training Program in Investigative Dermatology. Dr. Elmets received his M.D. degree from the University of Iowa in 1975 and completed residencies in Internal Medicine (1978) and Dermatology (1980) and an Immunodermatology Fellowship (1982). He is Board Certified in Internal Medicine, Dermatology, and Immunodermatology and is recertified in Dermatology. Before moving to UAB, he was Assistant, Associate and Full Professor of Dermatology at Case Western Reserve University (1982-1997) and was an active member of the Cancer Center at that institution.

Dr. Elmets has been a leader in investigating the biologic effects of ultraviolet radiation and of polyaromatic hydrocarbon carcinogens on the skin, and on acquired and adaptive immunity as it relates to skin cancer development. Translational studies have included the use of cyclooxygenase inhibitors and DNA repair enzymes as chemopreventive agents for nonmelanoma skin cancer.  Preclinical investigation in animal models has focused on the development of vaccination strategies for the prevention of polyaromatic hydrocarbon-induced skin cancers.  His research has been published in critically reviewed journals, and he has established a national and international reputation in the areas of immunodermatology, photobiology and skin cancer chemoprevention.  Dr. Elmets’ contribution to these areas has been acknowledged by the award of several NIH, EPA, DOD and VA research grants, and he has received continuous NIH funding since 1983. His expertise in these research disciplines has also been recognized by his inclusion on the editorial boards of Cancer Prevention Research; the Journal of Immunology; the Journal of Investigative Dermatology; Photochemistry and Photobiology; Experimental Dermatology; Photodermatology, Photoimmunology and Photomedicine; the Journal of Dermatological Sciences; and the Journal of the American Academy of Dermatology. He has co-edited three books on photoimmunology and phototherapy. He has served on the Chemical Pathology Study Section of the National Institutes of Health and was a member of Veterans Administration Merit Review Subcommittee for Oncology.

Clinton J. Grubbs, Ph.D., is a basic scientist with a primary research interest in the chemoprevention of urinary bladder and mammary cancers. His major area of research is the identification of nutrient and non-nutrient agents that exhibit efficacy in the prevention of these cancers. He is a Professor in the UAB Department of Surgery and a Senior Scientist in the UAB Comprehensive Cancer Center.  Dr. Grubbs received his doctoral degree from the University of Tennessee Medical Units in Memphis, Tennessee in 1973. He also completed a two year postdoctoral fellowship in biochemistry at the University of Tennessee Medical Unit. From 1975 to 1979, he was a senior physiologist at the Illinois Institute of Technology in Chicago, Illinois.  After six years at Southern Research in Birmingham, he joined the faculty at UAB in the Department of Nutrition Sciences, and in 2000 transferred to the Department of Surgery.

In 1987, he was awarded Master Agreements from the NCI for in vivo screening of chemopreventive agents and for the evaluation of the efficacy of potential preventive compounds. The agreements, now a Prime Contractor, continue to be active. Through this funding, Dr. Grubbs has established subcontracts for chemoprevention research with five universities and research institutes in the United States. Dr. Grubbs has established a national and international reputation in the preclinical evaluation of chemopreventive agents in cancer.  His research is published in widely read peer-reviewed journals.  At UAB, he served as Chair of the UAB IACUC Committee from 1987-2001. He also served on the PREVENT Review Panel of the National Cancer Institute for more than 10 years.

Leadership Activities:

  • To enhance the knowledge base and to facilitate the understanding of the most recent developments in cancer prevention, the Cancer Chemoprevention Program has monthly meetings. Both Drs. Elmets and Grubbs co-direct these meetings.  During these meetings, speakers within and outside of the Cancer Chemoprevention Program discuss their work. This is followed by an informal discussion about collaborations and funding opportunities. The monthly meetings serve as a catalyst for discussions as well as intra- and inter-disciplinary collaborations. Evidence of the effectiveness of these monthly meetings in catalyzing team science is manifest in the high proportion of intra- and inter-programmatic peer-reviewed research papers which comprise 33% and 47% of the total number of articles, respectively.
  • Both Drs. Elmets and Grubbs meet with each member of the Cancer Chemoprevention Program twice a year, and more often when necessary, to discuss their progress, problems and opportunities with respect to chemoprevention research.
  • Both directors meet regularly with Dr. Partridge and the CCC administrative staff about funding options, space, and resource needs.
  • UAB participates in the consortium early phase human chemoprevention trials led by the University of Wisconsin (UW); Dr. Elmets serves as the lead investigator for this consortium and serves as the primary conduit for the collaboration existing between UW and UAB.
  • Similarly, Dr. Grubbs is a Prime Contractor for the NCI which awards preclinical work assignments to investigators both at UAB and other institutions.
  • In addition, Dr. Grubbs has established a strong liaison with the Chemoprevention Agent Development Research Group of the Division of Cancer Prevention at the NCI. Dr. Grubbs serves as a liaison between UAB and the NCI Division of Cancer Prevention with 2-3 visits to NCI annually.
  • Dr. Grubbs has established four laboratories for the preclinical evaluation of agents for chemoprevention activity: 1) animal models; 2) histopathology; 3) biochemistry; and 3) pharmacology-toxicology. These laboratories are available to cancer center members in general, and more specifically to investigators in the Cancer Chemoprevention Program. These laboratories serve as an incubator for intra- and inter-programmatic collaboration.
  • Both Drs. Elmets and Grubbs have been active in the recruitment of several new members to the Chemoprevention Program.
  • Drs. Elmets and Grubbs work together to facilitate the development of productive intra-programmatic and inter-programmatic interactions between cancer center investigators. Examples are discussed specifically in the Intra- and Inter-Programmatic Sections (Sections D and E), as well as woven throughout the section that addresses Accomplishments of the Cancer Chemoprevention Program, which are largely a product of team science.

Contact Information:

Co-Leader: Craig Elmets, M.D.
Email: celmets@uab.edu
Phone: (205) 934-5188

Co-Leader: Clinton Grubbs, Ph.D.
Email: clintongrubbs@uab.edu
Phone: (205) 934-6384

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