Lipid May Provide a Rapid Method for Detecting MDR Breast Cancers

CHICAGO--Investigators at the John Wayne Cancer Center, Santa Mon-ica,Calif, have discovered a lipid that appears to be unique to multidrug-resistant(MDR) cancers.

Because the lipid, glucosylceramide, can be identified in a matter ofhours by lipid chromatography, it may provide an easy way of detectingmalignancies that will not respond to chemotherapy, Anthony Lucci, MD,said at the Society for Surgical Oncology's Cancer Symposium.

Glucosylceramide was first identified in the MCF-7 doxorubicin-resistantbreast cancer cell line, Dr. Lucci noted, but was absent from wild-type,non-drug-resistant breast cancer strains. It has been identified in twoother MDR cancer cell lines--KB-V-1 epidermoid carcinoma and OVCAR-3 ovariancarcinoma.

It also was found in all drug-resistant tumor tissue samples from agroup of AJCC stage IV melanoma patients and stage IV breast cancer patients.In every case, however, the lipid was not present in tissue samples fromstage IV melanoma or breast cancer patients who had at least a partialresponse to chemotherapy.

When the researchers assessed the rate of synthesis of glucosylceramide,they found a ninefold higher rate of formation in MDR cell lines. Theyconcluded, therefore, that glucosylceramide is an attractive new markerfor multidrug resistance. "It is not something that usually accumulatesin cells, but it is found in all MDR cell lines tested and in patientswith a clinical history of unresponsiveness to chemotherapy," Dr.Lucci said.

He noted that this pilot study involved a small number of patients,and the marker is currently being evaluated prospectively in a larger numberof advanced-stage breast cancer patients.