Multidrug resistance and malignancy - An article in the May 15, 1996
issue of Cancer Research examined the question of whether the two
causes for failure of present treatment for osteosarcoma, drug
resistance and metastatic spread, were related. Researchers from
the Orthopedic Institute in Bologna, Italy, looked at the gene
called MDR that makes cells resistant to drugs by producing a
protein, P-glycoprotein, that transports drugs out of cells,
leaving the drug levels inside the tumor cells too low to cause
cell death. They reported that drug-resistant experimental tumor
cell lines expressing P-glycoprotein were generally deficient in
the cancer-like feature of drug-sensitive cells, being less able
to invade tissues and to form metastases. In their osteosarcoma
patients being treated with chemotherapy, lung metastases
occurred much sooner in those whose tumor cells were deficient in
P-glycoprotein than in those whose cells overexpressed the
protein. Also, at the time of diagnosis, excess P-glycoprotein
was more common among patients with local disease than among
those with metastases. Any association between P-glycoprotein
overexpression and poor clinical outcome appears to be due to
drug resistance and not to increased ability of resistant tumors
to form metastases. (Scotlandi, Cancer Research 56:2434, 1996)
Editor's Comment: - These findings are in line with many
experimental studies, which have shown that when cells become
resistant to drugs, it is often at a cost in terms of some sort
of growth disadvantage as compared with the original, so-called
wild-type. Most often the resistant cells grow more slowly,
probably due to metabolic adjustments that must be made as part
of the resistance mechanism, but from the "cell's standpoint"
some growth is better than none or than being killed by the drug.
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