IN VITRO DRUG SENSITIVITY TESTING OF MARROW METASTASES

HUMAN TUMOR CLONOGENIC ASSAYS (HTCA'S) ARE USED TO TEST TUMOR SPECIMENT IN VITRO AGAINST CHEMOTHERAPEUTIC DRUGS. CURRENTLY, USE OF HTCA'S IS LIMITED TO TUMOR SPECIMENS OBTAINED AT DIAGNOSIS OR AT OVERT RELAPSE. AN IDEAL SITUATION WOULD BE TO TEST METASTATIC CELLS PRIOR TO RELAPSE BEFORE DRUG RESISTANCE IS A FACTOR. THIS SITUATION IS FEASIBLE BY OBTAINING SMALL NUMBERS OF TUMOR CELLS FROM THE BONE MARROW OF PATIENTS WITH A VARIETY OF SOLID TUMORS. THE APPLICANTS HAVE DEVELOPED AN HTCA THAT PERMITS THE CLONOGENIC GROWTH OF TUMOR CELLS FROM THE BONE MARROW OF BREAST CANCER PATIENTS. THE ADVANTAGES OF THIS HTCA METHOD ARE: 1) TESTING CAN BE PERFORMED AT ALL STAGES OF DISEASE WHEN METASTATIC CELLS ARE PRESENT IN MARROW; 2) SENSITIVITY AND SPECIFICITY MAY BE IMPROVED BECAUSE METASTASES IN MARROW MAY REPRESENT AN AGGRESSIVE CLONE OF CELLS THAT ARE REFLECTIVE OF OTHER SYSTEMIC METASTASES; AND 3) SERIAL TESTING CAN BE PERFORMED TO IDENTIFY EMERGING DRUG RESISTANCE AS TREATMENT PROCEEDS. THIS MARROW HTCA IS ALSO FELT TO BE IDEAL FOR IN VITRO PHARMACOLOGIC TESTING OF NEW COMPOUNDS AGAINST HUMAN METASTATIC TUMOR CELLS IN THEIR NATURAL MARROW MICROENVIRONMENT AND FOR VERIFICATION OF TUMOR CELL REMOVAL BY VARIOUS MARROW-PURGING TECHNIQUES.