DIFFERENCES IN DRUG SENSITIVITY AMONG TUMOR-CELLS FROM PARENTAL TUMORS, SELECTED VARIANTS, AND SPONTANEOUS METASTASES

Abstract

Eradication of drug-resistant tumor foci is essential to the successful treatment of metastasis with chemotherapeutic agents. The in vitro sensitivity was studied to a variety of chemotherapeutic agents of tumor cells from parental tumors, from their in vitro-cloned populations, and from their spontaneous metastases. Three murine tumors were studied: the B16 melanoma; the K-1735 melanoma; and the UV-2237 fibrosarcoma. The in vitro drug sensitivity of cells from the A-375 human melanoma and its various subpopulations was examined. The drugs used in these studies were Adriamycin, 4''-(9-acridinylamino)methanesulfon-m-anisidine, bleomycin, 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide, vincristine and vindesine. The growth-inhibiting activity of the drugs was recorded in values which were derived from plotting the logarithm of the drug concentration vs. the growth rate (percentage of control) of the treated cells and which determined the molar concentration of drugs necessary to reduce doubling by 50%. Differences in drug response exist among cells populating a parental tumor (in vitro cloned), between the parental line and its metastatic subpopulations (in vivo-selected lines), and among the various spontaneous metastases. These extensive differences in drug sensitivity could have profound implications for the treatment of metastases with cytotoxic drugs.