Abstract 5541: Natural products as possible anti-cancer agents for digestive malignancies

Introduction: Natural products are evolutionarily designed and contain more complex and challenging structures than synthetic compounds. Historically, during the 1950s and 1960s anti-cancer agents for digestive malignancies, such as mitomycin and bleomycin, were isolated from actinobacteria; and then anti-cancer agents from plants, which include taxanes and camptothecin, were isolated. Their derivatives were also developed and are in clinical use. Purified ingredients and crude extracts from natural products such as PSK and those of Chinese herbal medicines are also in clinical use. Since the 1980s industries and academia have been focusing on strategies for development of targeted agents by screening a library of synthetic compounds; but recently natural products have been refocused on as a rich repository for drug discovery. Methods: To summarize the information of natural products as novel anti-cancer agents for digestive malignancies as well as their information in clinical trials, we surveyed literatures in the NCBI PudMed database and clinical trials registered in the FDA database, using keywords such as “natural products”, “anti-cancer agents”, and “digestive malignancy” or each of the malignancies (“esophageal cancer”, “stomach cancer”, “colorectal cancer”, “pancreatic cancer”, “biliary cancer” and others). We further classified the products on their chemical structures and their origins depending on types of drug-producing organisms. Results: With the above surveys, over 600 natural products were listed as possible substances as anti-cancer agents of digestive malignancies in preclinical development. Over 75% of the products were from plants. Their main structures consist of flavonoids, lignans, xanthones and others. The products from terrestrial animals and marine organisms were also listed. Curcumin, talaporfin sodium, eicosapentaenoic acid, resveratrol and other products are under clinical trials. Discussion: Despite many efforts, natural products have not been fully investigated for discovery of anti-cancer agents. New technologies having been applied for synthetic compounds, such as those for cultivation of drug-producing organisms, extraction and purification of substances, appreciation of targets, utilization of genomics information, and utilization of bioinformatics and cheminformatics with in silico analysis, can surely be utilized for anti-cancer drug discovery with natural products for digestive malignancies. Citation Format: Koh Miura, Masayuki Satoh, Makoto Kinouchi, Kuniharu Yamamoto, Yasuhiro Hasegawa, Yoichiro Kakugawa, Masaaki Kawai, Kiyoshi Uchimi, Hiroki Aizawa, Hiroto Sakurai, Tsuneaki Fujiya. Natural products as possible anti-cancer agents for digestive malignancies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5541. doi:10.1158/1538-7445.AM2015-5541