Biomolecular markers as intermediate end points in chemoprevention trials of upper aerodigestive tract cancer

Head-and-neck squamous-cell cancer (HNSCC) is an important public-health pr oblem, accounting for approximately 40,300 new cancer cases and 12,000 canc er deaths annually in the United States (Greenlee et (al., 2000), Patients with early-stage disease are often cured with surgery or radiotherapy but a re at high risk for second primary tumor (SPT) development (Lippman and Hon g, 1989), and the majority of patients present with advanced disease, for w hich the outcomes have not markedly improved despite advances in combined-m odality therapy (Vokes et al,, 1993). HNSCC arises from transformation of t he genetic material of normal cells, followed by successive genetic alterat ions in a multistep fashion, leading to clonal evolution of progeny cells w ith a proliferative advantage (Vogelstein and Kinzler, 1993), induced by th e Field-wide exposure to tobacco carcinogens (Slaughter et (II., 1953). Che moprevention aims at reversal of this process through re-regulation of grow th and differentiation and possibly elimination of genetically and phenotyp ically aberrant clones. Chemoprevention studies in upper aerodigestive trac t (UADT) cancers are based on these fundamental premises and the identifica tion of molecular genetic and biologic cellular changes. These alterations represent biomarkers of the carcinogenesis process and ultimately, if valid ated, could serve as intermediate end points for these studies. Int. J, Can cer 88:852-855, 2000, (C) 2000 Wiley-Liss, Inc.