INTEGRATED CLINICAL AND BASIC STUDIES RELATED TO CIRCUMVENTING NONSMALL CELL LUNG-CANCER DRUG-RESISTANCE

Consideration of a range of clinical and basic studies conducted at th e National Cancer Institute which explore the nature of the tumor biol ogy of lung identify the limitations of using chemotherapy for the tre atment of advanced lung cancer. No single mechanistic explanation for lung cancer's chemoresistance is apparent, although considerable infor mation about the biology of lung cancer and some of its clinical conse quences have been elucidated. In contrast to previous works from our g roup, this presentation will focus principally on studies of the natur e of drug resistance with non-small cell cancer. An alternative combin ed modality strategy for lung cancer control is to focus on epithelial progression of lung cancer using local modalities while it is still c onfined to the bronchial epithelium. Particular high risk populations may be appropriate to determine if local tools such as photodynamic la ser therapy can be effective in this application. To deal with the und erlying biochemical perturbations resulting from critical exposure of the bronchial epithelium to carcinogens, rational biochemical interven tion with 13 cis retinoic acid are being evaluated in several clinical trials. An evolution towards more effective lung cancer control may i nvolve the combined modalities of laser ablation of accessible dysplas tic epithelium and chronic administration of intervention agents, such as retinoids, to neutralize cancer promotion dynamics in the more rem ote areas of the lung epithelium.