Retinoids in lung cancer chemoprevention and treatment

In this review, we aim to synthesize the emerging picture of retinoids in l ung cancer through a summary of ongoing investigations in biology, chemopre vention and therapy settings, in an attempt to clarify the possible role of these agents in such a disease. Early work in head and neck cancer has evi denced the capability of retinoids to interrupt field carcinogenesis by rev ersing premalignant lesions and decreasing the incidence of second primary tumors (SPTs). At this time, the completed randomized trials in lung cancer have failed to demonstrate an evident chemopreventive effect of the tested agents on different study end points, although both a marginally significa nt benefit of retinol palmitate in time-to-development rates for smoke-rela ted SPTs and a potential preventive effect of retinol supplementation again st mesothelioma in selected populations of asbestos-exposed workers have be en recently reported. Concerning the role of retinoids in lung cancer treat ment, a moderate activity of 13-cis-retinoic acid (13cRA) or all-trans-reti noic acid (ATRA) as single agents has been reported in small series of adva nced, mostly pretreated lung cancer patients. More encouraging findings der ive from combination studies, in which retinoids, especially ATRA, are adde d to either alpha-interferon or chemotherapy and radiotherapy. Major recent advances have been made towards the understanding of retinoids mechanisms of action; at this regard, the role of RAR-beta basal or treatment-induced levels seems to be of particular interest as intermediate end point and/or independent prognostic factor, besides their known importance in lung carci nogenesis. Future research for chemopreventive and therapeutic programs wit h retinoids in lung cancer should be focused on the investigation of new ge neration compounds with a specificity for individual retinoid nuclear recep tors. Such selective molecules may have a greater activity against lung can cer, with a more favourable toxicity profile, as recently suggested by our preliminary data on Ro 41-5253.