Cancer Chemoprevention

elmets_thumbnail
Craig Elmets, M.D.
– Co-Leader


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.

 

Leave a Reply