[From cancer prevention to cancer treatment].
Cancer is a common life-threatening disease. Prevention and therapy of the disease are the desire of everybody. This paper summarizes our attempt to the tough challenge. Chronologically we began the study of carcinogenesis, and then turned to the research of anticancer agents. Identification of food mutagens was extensively studied. Once they were identified, the mechanism of nucleic acid modifications by these mutagens had been studied. The modification study gave information on the nucleic acid modification by mitomycin and bleomycin. The structure-activity relationship study of phorbol esters and teleocidines whose tumor promotion is epigenetic, was extensively studied. On the other hand, retinoic acid, a vitamin A metabolite, suppresses the epigenetic tumor promotion. This suggests that an epigenetically active compound rather than a cytotoxic anticancer agent can be used for tumor suppression. In the retinoid research, we found a number of characteristic new active substances which may be of therapeutic use: some of them are in the clinical trial stages in the field of dermatology and cancer. During the chemical study of retinoids, we encountered the retinoic acid receptor, coded by the retinoic acid receptor (RAR) gene which had just reported. Further retinoid research yielded retinoids antagonists, and then RXR(retinoic acid-X-receptor)-agonists and RXR-antagonists. These ligands have a big potential in the therapy of diabetes and obesity.
Shudo
K
K
Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
D000818:Animals; D000970:Antineoplastic Agents; D001565:Benzoates; D001761:Bleomycin; D002273:Carcinogens; D003984:Dibenzazepines; D005504:Food Analysis; D006801:Humans; D008024:Ligands; D008235:Lyngbya Toxins; D016685:Mitomycin; D009153:Mutagens; D009369:Neoplasms / Q000517:prevention & control* / Q000628:therapy*; D010703:Phorbol Esters; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000037:antagonists & inhibitors; D047488:Retinoid X Receptors; D012176:Retinoids; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors / Q000819:agonists / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D001565:Benzoates; D002273:Carcinogens; D003984:Dibenzazepines; D008024:Ligands; D008235:Lyngbya Toxins; D009153:Mutagens; D010703:Phorbol Esters; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; C061133:tamibarotene; D001761:Bleomycin; C104181:HX 600; C022176:teleocidins; D016685:Mitomycin