Abstract
The human tumor cloning assay as described by Hamburger and Salmon was utilized to study the direct antitumor effects of the hypoxic cell sensitizer misonidazole (MISO). Cells from 106 tumor specimens directly obtained from patients were exposed to MISO at clinically achievable drug concentrations (0.5 mM). Of 30 evaluable tumors, seven specimens (23%) showed a ≤50% decrease of TCFU's. In vitro sensitivity to MISO was noted in human breast cancer, renal cancer, non small-cell lung cancer, and adenocarcinoma of unknown primary site. A dose response relationship was demonstrated in a subset of experiments including 6 patient's tumors and one human breast cancer cell-line. An analysis relating MISO sensitivity or resistance to the results obtained with other, simultaneously tested standard anticancer drugs indicated that tumors exhibiting a ≤50% decrease of TCFU's in the presence of MISO were also likely to be sensitive to other cytotoxic drugs. In summary, our data suggest that the 'nitroimidazoles' may exert clinically significant direct antitumor effects in individual tumors. The human tumor cloning assay may have potential to evaluate these direct effects of MISO-analogues and other new radiosensitizers currently being tested in clinical trials.
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