CELLULAR PARAMETERS OF DRUG SENSITIVITY IN HUMAN TUMORS IN VITRO

AN IMPORTANT NEED IN CANCER CHEMOTHERAPY IS A HIGHLY PREDICTIVE IN VITRO CHEMOSENSITIVITY ASSAY. A MAJOR IMPEDIMENT TO THE DEVELOPMENT OF SUCH A TEST HAS BEEN THE LACK OF A SUITABLE SYSTEM FOR CULTURING HUMAN TUMORS IN VITRO SO THAT THEY REPRESENT TUMORS IN THE IN VIVO STATE. TO OVERCOME THIS PROBLEM, ANTICANCER, INC. HAS RECENTLY DEVELOPED A TUMOR CULTURE SYSTEM FOR THE IN VITRO GROWTH OF DIVERSE HUMAN TUMORS IN AN IN VIVO-LIKE WAY. THIS SYSTEM ALLOWS OVER 75% OF EXPLANTED TUMORS TO BE GROWN FOR PERIODS OF TIME THAT AVERAGE OVER 90 DAYS. THE TUMORS ARE EXPLANTEDON GELS DERIVED FROM PIGSKIN RICH IN EXTRACELLULAR-MATRIX BASEMENT-MEMBRANE COMPONENTS SUCH AS VARIOUS COLLAGENS AND LAMININ. THIS TUMOR CULTURE SYSTEM ALLOWS THE READY MEASUREMENT OF DNA AND PROTEIN SYNTHESIS IN INDIVIDUAL CELLSWITHIN TUMORS BY AUTORADIOGRAPHIC TECHNIQUES. THIS RESEARCHWILL UTILIZE THIS METHOD OF HUMAN TUMOR CULTURE TO DETERMINETHE CRITICAL PARAMETERS FOR IN VITRO DRUG SENSITIVITY TESTING WITH THE EVENTUAL GOAL OF DETERMINING WHICH PARAMETERS ARE THE MOST PREDICTIVE OF THE IN VIVO RESPONSE OF TUMORS TO DRUGS. IN THIS LIGHT, CHEMOTHERAPEUTIC DRUGS WILL BE TESTED FOR THEIR EFFECT ON DNA SYNTHESIS, PROTEIN SYNTHESIS, AND CELL VIABILITY STAINING IN A QUANTITATIVE MANNER. IN CONCERT WITH THE ABOVE EXPERIMENTS, ANTIBODIES WILL BE USED TO DETERMINE SPECIFIC CELL-TYPE MARKERS WITHIN THE VARIOUS TYPES OF HUMAN TUMOR CULTURES GROWING IN VITRO IN ORDER TO IDENTIFY THE ESSENTIAL NATURE OF CELLS WITHIN TUMORS. THIS IS ESPECIALLY CRITICAL FOR MEASURING DRUG SENSITIVITIES. TUMORS OF THE BREAST, LUNG, AND, COLON WILL BE EMPHASIZED. PATIENT RESPONSE DATA WILL BE OBTAINED AND CORRELATED TO IN VITRO CHEMOSENSITIVITIES TO DETERMINE THE MOST PREDICTIVE IN VITRO PARAMETERS. THE EXPERIMENTS PROPOSED HERE SHOULD ALLOW A MAJOR ADVANCE TOWARD THE GOAL OF A COMMERCIAL DRUG SENSITIVITY TEST.