NEWER OPTIONS FOR TREATING DRUG-RESISTANT (MDR-CELLS USING PHOTORADIATION THERAPY() CANCER)

Emergence of drug resistance with conventional cytotoxic therapy is a major challenge towards the curability of many cancers, especially in patients undergoing autologous BMT with ex-vivo purged hematopoietic s upport. We have explored the potential role of photoradiation therapy in purging hematopoietic stem cells of various hematological malignanc ies. Benzoporphyrin derivative, monoacid ring A (BPD-MA), dihematoporp hyrin ether (DHE), and MC540 were evaluated for the ''ex-vivo'' purgin g of residual tumor cells from autologous bone marrow (BM) grafts. BPD -MA and DHE photosensitizing activity was tested against two human lar ge cell lymphoma cell lines and colony forming-unit leukemia (CFU-L) d erived from patients with acute myelogenous leukemia (AML). In mixing experiments four log elimination of tumor cell lines was observed afte r 1 hr of incubation with BPD-MA or DHE followed by white light exposu re. By comparison, using the same concentration of BPD-MA or DHE, the mean recovery of normal BM progenitors was 4-5.2% for granulocyte-macr ophage colony forming unit (CFU-GM) and 5-9.8% for burst forming unit erythroid (BFUE). The T lymphoblastic leukemia cell line CEM and its v inblastine (VBL)-resistant subline CEM/VBL100, along with the acute pr omyelocyte leukemia cell line HL-60 and its vincristine (VCR)-resistan t subline HL-60/VCR, were also tested. Our results demonstrated the pr eferential cytotoxicity of BPD-MA and DHE toward neoplastic cell lines and CFU-L from AML patients. In addition, DHE was slightly more effec tive in purging tumor cells expressing the p-170 glycoprotein. These r esults suggest that photoradiation would be useful for ''ex-vivo'' pur ging of malignant cells. Other methods to deal with decreasing drug re sistance are also detailed.