title: Biomolecular markers as intermediate end points in chemoprevention trials of upper aerodigestive tract cancer.
abstract: Head-and-neck squamous-cell cancer (HNSCC) is an important public-health problem, accounting for approximately 40,300 new cancer cases and 12,000 cancer deaths annually in the United States (Greenlee et al., [2000]). Patients with early-stage disease are often cured with surgery or radiotherapy but are at high risk for second primary tumor (SPT) development (Lippman and Hong, [1989]), and the majority of patients present with advanced disease, for which the outcomes have not markedly improved despite advances in combined-modality therapy (Vokes et al., [1993]). HNSCC arises from transformation of the genetic material of normal cells, followed by successive genetic alterations in a multistep fashion, leading to clonal evolution of progeny cells with a proliferative advantage (Vogelstein and Kinzler, [1993]), induced by tobacco carcinogens (Slaughter et al., [1953]). Chemoprevention aims at reversal of this process through re-regulation of growth and differentiation and possibly elimination of genetically and phenotypically aberrant clones. Chemoprevention studies in upper aerodigestive tract (UADT) cancers are based on these fundamental premises and the identification of molecular genetic and biologic cellular changes. These alterations represent biomarkers of the carcinogenesis process and ultimately, if validated, could serve as intermediate end points for these studies.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Papadimitrakopoulou
authors.forename: W K
authors.initials: WK
authors.lastname: Hong
mesh_terms: D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D002986:Clinical Trials as Topic; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000378:metabolism; D020868:Gene Silencing; D019942:Genes, p16 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D005819:Genetic Markers; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D019656:Loss of Heterozygosity; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012176:Retinoids / Q000627:therapeutic use*
chemical_list: D016588:Anticarcinogenic Agents; D005819:Genetic Markers; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D066246:ErbB Receptors