The objective of this program of the NCDDG, is to discover natural products produced by marine invertebrate animals and/or associated microorganisms which display activity in Wyeth's oncology drug screens. Specifically, this program will: Collect a variety of marine invertebrate animals (~ 300 annually) from different geographical locales and ecological niches in the Philippines and the South Pacific. In addition, microorganisms from marine habitats in Fiji and the surrounding USP region will be isolated and cultured at Wyeth. Microorganisms from the Philippines will be isolated and cultured by Dr. Gomez's group at UP-MSI. All samples will be screened in Wyeth's oncology screens. The organisms that display activity will be re-fermented and supplied for isolation studies. The details of these studies are provided in Drs. Carter and Greenstein's section for the work to be done at Wyeth, and Dr. Gomez's section for the work to be done at UP-MSI. Perform bioassay-guided isolation of active constituents from the extracts of the above mentioned organisms, determine their structures, and provide these metabolites for biological evaluation. Organisms will be prioritized on the basis of screening results from Wyeth's mechanism-based screening protocol. Purified metabolites will be further evaluated in secondary assays to define mechanism of action, and for in vivo efficacy against human solid tumors implanted in nude mice.