P2.03 Combination of Endothelium Directed Drugs and Cyclophosphamide - A Comprehensive Approach in Cancer Treatment

Abstract

ABSTRACT The ability of cancer cells to detach from the primary tumor, then to migrate through the vascular system and finally to colonize distant tissues and form drug- resistant and irremovable lesions still remains the leading death cause among cancer patients. Therefore a therapeutic approach based on a combined treatment directed against the tumor growth as well as the invasive potential of cancer cells may be a promising strategy for a comprehensive anticancer therapy. Pyridinium salts such as 1-methylnicotinamide chloride (MNA) and its derivative 1,4- dimethylnicotinamide chloride (1,4-DMP) were previously shown to influence the metastatic process when given both alone as well as in a combination with cytostatic or antiplatelet drugs. Such observation encouraged us to further investigation of their activity in a triple drug combinations. In our recent study carried out in the orthotopically implanted 4T1 mouse mammary gland cancer cells we have shown that 1,4-DMP exceeds the activity of MNA when salts are given in a combination with cyclophoshamide and antiplatelet drug clopidogrel. 1,4-DMP not only preserved anticancer activity of applied cytostatic (tumor growth inhibition remained at the level of 40-55 % from the 15th until the last day of the experiment) but also decreased the number of lung metastasis in 80 % when compared to the control group of animals (P