NEW TOPICAL DRUGS AGAINST SKIN CANCER

THE RESEARCH IS INTENDED TO DEVELOP TOPICAL FORMULATIONS OF TWO NEW 2-2-DIMETHYLPHOSPHORAZIRIDINE ANTINEOPLASTIC AGENTS AND TO EVALUATE THESE FORMULATIONS IN-VIVO IN A MURINE SQUAMOUS CELL CARCINOMA MODEL SYSTEM OF HUMAN CANCER. THESE TWO COMPOUNDS WERE CHOSEN BECAUSE OF THEIR ABILITY TO INHIBIT THE GROWTH OF HUMAN EPIDERMAL CARCINOMA CELLS AT CONCENTRATIONS THAT DO NOT AFFECT NORMAL HUMAN KERATINOCYTES, AND FOR THEIR UNIQUE AND POTENTIALLY ADVANTAGEOUS PHARMACOLOGICAL ACTIVITIES (E.G. HYDROLYTIC STABILITY, LOW CNS TOXICITY). SPECIFICALLY, THESE COMPOOUNDS WILL BE SYNTHESIZED AND FORMULATED INTO TOPICAL CREAMS THAT WILL VARY IN COMPOSITION TO REDUCE THE POTENTIAL FOR HYDROLYTIC (OR OTHER) DECOMPOSITION OF EACH DRUG. ONCE THE MOST STABLE DRUG FORMULATIONS ARE DEVELOPED, INCREASING AMOUNTS OF EACH COMPOUND IN THOSE FORMULATIONS WILL BE APPLIED TOPICALLY TO MICE BEARING CARCINOGEN INDUCED SQUAMOUS CELL CARCINOMAS AND THE AVERAGE TUMOR SIZE AND WEIGHT WILL BE DETERMINED ACCORDINGLY. FUTURE STUDIES IN PHASE II WILL INVOLVE MORE EXTENSIVE INVESTIGATIONS OF THE IN-VIVO PHARMACOLOGICAL AND TOXICOLOGICAL EFFECTS OF THESE TREATMENTS IN PREMALIGNANT AND METASTATIC BASAL AND SQUAMOUS CELL CARCINOMA MODELS AS WELL AS OTHER MODELS OF PAPULOSQUAMOUS DISEASE. THE ULTIMATE GOAL OF THIS RESEARCH IS SUBMISSION OF IND APPLICATIONS FOR THESE FORMULATIONS TO THE FDA FOR COMMERCIALIZATION.