Pancreatic cancer is the 4th most common cause of cancer deaths in the USA with fewer than 3% of the patients surviving 5 years. In the absence of a marked improvement in detection methods or prevention, it is not probable that the majority of tumors of this type will remain beyond the control capability of surgery, radiation therapy or both. Thus, chemotherapy holds the most therapeutic promise in spite of the fact that positive results with current agents have been limited. Two research approaches will be used: 1st, the evalution of clinically available drugs and especially Phase I-II agents against two transplantable pancreatic ductal adenocarcinomas (Panc 02, 03) of mice. Active single agents will then be evaluated in selected combinations in the search for therapeutic potentiation and clinical application; 2nd, A New Drug-Discovery effort targeted toward the isolation of agents with more activity against pancreatic tumors than leukemias will be initiated. This drug discovery effort has been made possible by the development of a cost-effective prescreen assay that allows the preferential selection of agents with activity against pancreatic tumor cells. For this assay both L1210 and Panc 02 are plated in soft agar in the same dish to provide selectivity. Panc 02 is used because it is unresponsive to 34 different antitumor agents (in mice) and only marginally responsive to three others (thus mimicking many human tumors of this type). The technique is similar to the human tumor stem cell assay with the exception that the drug is not added to the cells. Instead, the drug is placed on a paper disk, which is then placed on top of the soft agar containing the two tumors. Depending on the innate sensitivity of the cells for the drug (and the concentration of the drug), a zone of inhibition of colony formation occurs. A differential zone between the two tumor types is readily detectable because each colony type is visually distinct. Thus, a drug producing a larger zone for Panc 02 than for the leukemia would be evaluated in mice. Both fermentation materials and synthetics are used in this assay, which can be carried out for 54/test agent.
