Session Plan Guidelines

Abstract submission to the 2009 NCI Translational Science Meeting will be available after invited participants have accepted the invitation and have registered for the meeting. If you have been invited or designated by an invited principal investigator to submit an abstract, please review the abstract submission process and instructions below. All abstracts must be submitted by Friday, August 14, 2009.

I. INSTRUCTIONS FOR ABSTRACT PREPARATION

1. The title of the abstract should be in uppercase and lowercase letters (please see illustration below)
2. List the author(s) full name using upper and lowercase letters and assign an affiliation number (i.e. John Doe (1), Jane Smith (2))
3. List the appropriate affiliation(s) (i.e. 1. National Cancer Institute, 2. University of California, Los Angeles)
4. The abstract should be single spaced and no more than 2500 characters (approximately 400 words)
5. Provide three keywords
6. Select at least one pathway, organ site, and population that best describes the science outlined within the abstract

During the abstract submission process, invited participants will be given the opportunity to paste their title, authors, and abstract into boxes that will NOT accept tables, charts, or images.

II. INSTRUCTIONS FOR PATHWAY CODING

1. Identify the pathway(s) most appropriate for your abstract
   • Biospecimen-based assessment tool (e.g. serum or tissue biomarker)
   • Image-based assessment tool (e.g. PET, MRI, optical)
   • Agent intervention (e.g. small molecule drug, inhibitory antibody)
   • Immune response modfication intervention (e.g. vaccine, cytokine)
   • Interventive device (e.g. radiation, surgical device)
   • Behavioral modification (e.g. nutrition, exercise)
2. Identify the pathway step(s) most appropriate for your abstract
   • Credentialing (e.g. scientific validation, need, feasibility)
   • Supporting tool (e.g. animal model, cohort, specimen repository)
   • Creation of modality (e.g. medicinal chemistry, multi-lab validation)
   • Preclinical development (e.g. toxicology, test on phantoms)
   • Phase I/II clinical trial
3. Identify the population(s) most appropriate for your abstract
   • Individuals at risk for cancer
   • Early stage cancer
   • Late stage cancer
   • Pediatrics
   • Minorities and Underserved
4. Identify the organ site(s) most appropriate for your abstract
   • Breast
   • Brain
   • Colorectal
   • GI (other than colorectal)
   • GU (other than prostate)
   • Gynecological
   • Head and neck
   • Hematopoietic
   • Lung
   • Prostate
   • Skin
   • Rare (sarcoma, etc)
   • All or most of the above
5. Check the appropriate boxes
   • There should be at least one “X” in each of the 3 sections
   • Try to limit the number of areas selected to those that are most relevant to the work presented in your abstract. Do not include previous work or future plans.
6. Submit 3 Keywords other than pathway, organ site, or population that describe the topic and scientific focus of your abstract.

Tips:

Basic versus Translational Research: Discovery research (fundamental as well as cancer-specific) occurs upstream of the pathways. The pathways start with the credentialing of a basic research discovery to determine if it is broadly applicable, important, and/or feasible enough to invest in its translation. For example, the discovery and characterization of a gene and determination of oncogenic activity in mice is discovery research. Early translational research, on the other hand, could involves modulating the gene in a large panel of cancer cell lines to determine if it is applicable to a particular form of cancer.

Translational versus Clinical Research: The pathways terminate in Phase I/II clinical trials, which are part of early translational research. Phase III clinical trials, by contrast, are considered to be part of late translational research (per the President's Cancer Panel definition). Correlative studies to clinical trials (including Phase III) that ask specific questions about cohort selection, response markers, etc. are considered early translational research.

More than one pathway: There are cases where both an assessment tool and an interventive device are developed concurrently, for example a biomarker of response to a particular intervention/treatment. The intervention pathways may include an assessment tool as a supporting tool in the pathway. If the intervention is novel and is being co-developed with an assessment tool, the intervention pathway is most relevant. If use of the assessment tool is novel and the intervention is well established, the assessment tool pathway is most relevant.

Continuum: Cancer research is a continuum, so distinctions between steps in a pathway are not always clear. There may be no right or wrong answer. The pathway grids are being used as tools to form multi-investigator/multi-disciplinary groups that have the potential to produce a product that completes an entire translational pathway.

III. EXAMPLE:

Early Phase Clinical Development of Polyphenon E for Cancer Prevention

H-H. Sherry Chow, David S. Alberts
Arizona Cancer Center, University of Arizona, Tucson AZ

Green tea has been shown to exhibit cancer preventive activities in preclinical studies. Its consumption has been associated with decreased risk of certain types of cancers in humans. The principal active constituents in green tea are believed to be green tea catechins. Of the green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has been shown to possess potent biological activities. Our initial clinical studies examined the safety and pharmacokinetics of pure EGCG extract and a defined green tea catechin extract (Polyphenon E). Polyphenon E contains 80-98% total catechins with EGCG as the main component accounting for 50-75% of the material. The oral bioavailability of EGCG is similar between the pure EGCG product and Polyphenon E at equivalent EGCG dose levels. Both products are well tolerated in healthy individuals following chronic administration at a daily dose that contains 800 mg EGCG. Polyphenon E was selected for further clinical development because it would be less costly for long term usage in the setting of cancer prevention and it contains other catechins which also possess cancer preventive activities.

Our follow up clinical studies showed that the bioavailability of EGCG was significantly increased after repeated green tea catechin dosing at high daily bolus doses, possibly due to inhibition of presystemic elimination of this catechin. In addition, we found that taking Polyphenon E on an empty stomach resulted in a greater than 3-fold increase in the systemic bioavailability of EGCG. We also demonstrated that chronic Polyphenon E administration has minimum effect on four major cytochrome P450 isozymes, suggesting that Polyphenon E administration is not likely to affect the pharmacokinetics of commonly used medications. Chronic Polyphenon E administration was shown to induce glutathione S-transferase (GST) activity and GST-pi level in blood lymphocytes with the most significant change observed in individuals with low baseline enzyme activity. Our data suggest that Polyphenon E intervention may enhance the detoxification of carcinogens in individuals with low detoxification capacity. We are currently conducting multiple early phase trials of Polyphenon E to evaluate its potential for prostate, lung, and cervical cancer prevention in high risk individuals. Supported by N01CN85719, N01CN25119, N01CN35158 from the National Cancer Institute, Division of Cancer Prevention

Keywords: green tea, Polyphenon E, cancer prevention

A Service of the National Cancer Institute