Following the presentations, the attendees discussed key questions and explored options to extend established research efforts into new interdisciplinary areas. Are mechanisms of tobacco-related carcinogenesis similar in all tobacco-related cancers? Are molecular alterations in NF-κB or signaling pathways in head and neck cancer also observed in bladder, pancreatic, kidney, and lung cancers? An integrated approach combining genomics, proteomics, and tissue microarrays would be best to address this question and could generate a uniform approach to prevent tobacco-related carcinogenesis.
The participants agreed that a better understanding of the molecular basis for addiction is essential. Specifically, nicotinic receptors are neglected components of tobacco-related research. Although the complexity of these receptors and poor experimental tools have limited study of these receptors in the past, researchers can now profile these receptors, modify their function, and detect the presence or absence of specific receptors using imaging techniques in vivo. These developments could allow the development of targeted addiction therapies and imaging of nicotinic receptors in target tissues during tobacco-related carcinogenesis.
Similar to the need to develop a better molecular understanding of addiction, defining mechanisms of actions for chemopreventive agents is required. Can unifying mechanisms be identified for chemically dissimilar chemopreventive agents? The ability of chemopreventive agents to prevent activation of carcinogens, rather than cause regression of preneoplastic lesions, is a laudable goal. This approach could provide intervention before the onset of carcinogenesis.
Finally, have reliable predictive factors for tobacco-related cancers been identified? Can these predictive factors be used to stratify patients for screening and/or early intervention? The recent localization of a major susceptibility locus influencing lung cancer risk to chromosome 6q23–25 offers the opportunity to coalesce a multidisciplinary team to study these rare families (4
). The identification of tumor suppressor genes or oncogenes that are altered within this region of the genome may help us to better understand the molecular alterations in sporadic, tobacco-related lung cancers. The participants agreed that augmenting genetic analyses with newer technologies, such as proteomics and molecular tissue analyses, could potentially add power to predictive studies. Applying state-of-the-art science to study addiction, tobacco-related carcinogenesis, and patients most at risk could provide benefit to individuals and society burdened by the effects of tobacco.