MONOCLONAL ANTIBODIES AGAINST PROGESTIN RECEPTOR ISOFORMS

ACCURATE IDENTIFICATION OF STEROID HORMONE RECEPTORS IN BREAST AND ENDOMETRIAL CANCER HAS BECOME AN ESSENTIAL PART OF THE CLINICAL MANAGEMENT OF THE CANCER PATIENT. THESE MEASUREMENTS PROVIDE PREDICTIVE INDICES OF THERAPEUTIC RESPONSE AND OFFER PROGNOSTIC INFORMATION OF THE CLINICAL COURSE. THE PRESENCE OF STEROID RECEPTORS, PARTICULARLY THE PROGESTIN RECEPTOR (PR), IN ENDOMETRIAL CARCINOMA IS CORRELATED WITH SUCCESSFUL HORMONAL TREATMENT RESPONSE AND DISEASE-FREE SURVIVAL. HENCE, ACCURATE MEASUREMENT OF PR IS ESSENTIAL TO THE SUCCESSFUL MANAGEMENT OF THESE PATIENTS. THE PRESENTLY AVAILABLE ASSAYS FOR PR DO NOT ACCURATELY IDENTIFY PATIENTS WITH ENDOCRINE RESPONSIVE TUMORS. THIS IS QUITE LIKELY DUE TO THE FACT THAT THE PR EXISTS IN DIFFERENT MOLECULAR FORMS, AND THAT THESE ISOFORMS CONTRIBUTE DIFFERENTLY TO THE CLINICAL COURSE OF THE TUMORS. IT IS THE GOAL OF THIS PROJECT TO GENERATE MONOCLONAL ANTIBODIES SPECIFIC FOR THESE VARIOUS ISOFORMS, AND TO SUBSEQUENTLY UTILIZE THESE ANTIBODIES TO DEVELOP ISOFORM SPECIFIC IMMUNOASSAYS FOR SPECIFIC PR ISOFORMS. THE AVAILABILITY OF SUCH ASSAYS SHOULD ALLOW FOR BETTER CHARACTERIZATION OF THESE BIOPSIES, SHOULD PROVIDE A MORE EFFICIENT PREDICTOR OF WHICH TUMORS ARE MOST LIKELY TO RESPOND TO ENDOCRINE THERAPY, AND SHOULD BE A MORE ACCURATE PROGNOSTIC INDICATOR OF THE SUBSEQUENT CLINICAL COURSE OF THE DISEASE.