Epithelial cancer of the aerodigestive tract is a tremendous problem throughout the world because of its increasing incidence and the difficulty of treating it once the tumor has developed. The overall goal of this program project grant is to develop effective chemopreventive approaches to reduce the incidence of human aerodigestive epithelial cancers, especially in those individuals who are at high risk. In order to make significant progress toward these goals, clinical studies and laboratory studies must be focused and closely integrated into a well-coordinated program. Specifically, this program encompasses three major directions: 1. Identification of Effective Chemopreventive Agents in Two Comprehensive Clllinical Trials: Project 1. Chemoprevention Trial to Prevent Second Primary Tumors with Low-Dose 13-cis Retinoic Acid in Head and Neck Cancer. Project 3. Chemoprevention Trial in Oral Premalignancy. 2. Identification and Determination of Relative Impact of Risk Factors for the Development of Aerodigestive Epithelial Cancers: Project 2. Genetic Susceptibility to Second Primary Tumors: The Quantitative Risk Assessment Model. 3. Understanding of the Fundamental Events of Biological Processes During Carcinogenesis and the Mechanisms of Action of Retinoids: Project 4. Field Cancerization: Cellular and Molecular Test of Hypothesis. Project 5. Molecular Determinants of Growth and Differentiation of Head and Neck Tumors. Project 6. Role of Nuclear Retinoic Acid Receptors in the Mechanism of Response of Malignant Oral Mucosa Cells to Retinoids. Five core components (Administration, Biostatistics/Data Management Center, Analytical Chemistry, Histology Laboratory, Nutritional Epidemiology, and Clinical Adherence) provide the structure and expertise required for the successful integration and execution of combined clinical trials and laboratory studies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA052051-10
Application #
6328916
Study Section
Subcommittee G - Education (NCI)
Program Officer
Szabo, Eva
Project Start
1991-08-05
Project End
2004-11-30
Budget Start
2001-02-05
Budget End
2004-11-30
Support Year
10
Fiscal Year
2001
Total Cost
$1,639,064
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Internal Medicine/Medicine
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Hildebrandt, Michelle A T; Lippman, Scott M; Etzel, Carol J et al. (2012) Genetic variants in the PI3K/PTEN/AKT/mTOR pathway predict head and neck cancer patient second primary tumor/recurrence risk and response to retinoid chemoprevention. Clin Cancer Res 18:3705-13
Lee, J Jack; Wu, Xifeng; Hildebrandt, Michelle A T et al. (2011) Global assessment of genetic variation influencing response to retinoid chemoprevention in head and neck cancer patients. Cancer Prev Res (Phila) 4:185-93
Zhang, Xiaofan; Yang, Hushan; Lee, J Jack et al. (2010) MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer. Carcinogenesis 31:2118-23
Wang, Jianming; Lippman, Scott M; Lee, J Jack et al. (2010) Genetic variations in regulator of G-protein signaling genes as susceptibility loci for second primary tumor/recurrence in head and neck squamous cell carcinoma. Carcinogenesis 31:1755-61
Wu, Xifeng; Spitz, Margaret R; Lee, J Jack et al. (2009) Novel susceptibility loci for second primary tumors/recurrence in head and neck cancer patients: large-scale evaluation of genetic variants. Cancer Prev Res (Phila) 2:617-24
William Jr, William N; Lee, J Jack; Lippman, Scott M et al. (2009) High-dose fenretinide in oral leukoplakia. Cancer Prev Res (Phila) 2:22-6
Papadimitrakopoulou, Vassiliki A; Lee, J Jack; William Jr, William N et al. (2009) Randomized trial of 13-cis retinoic acid compared with retinyl palmitate with or without beta-carotene in oral premalignancy. J Clin Oncol 27:599-604
Kawaguchi, Hidetoshi; El-Naggar, Adel K; Papadimitrakopoulou, Vali et al. (2008) Podoplanin: a novel marker for oral cancer risk in patients with oral premalignancy. J Clin Oncol 26:354-60
Wu, Xifeng; Gu, Jian; Dong, Qiong et al. (2006) Joint effect of mutagen sensitivity and insulin-like growth factors in predicting the risk of developing secondary primary tumors and tumor recurrence in patients with head and neck cancer. Clin Cancer Res 12:7194-201
Lippman, Scott M; Lee, J Jack (2006) Reducing the ""risk"" of chemoprevention: defining and targeting high risk--2005 AACR Cancer Research and Prevention Foundation Award Lecture. Cancer Res 66:2893-903

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