In vitro drug screening and individualized treatment planning for cancer patients.
We have developed an in vitro screening test for anticancer agents, using monodispersed tumor cells derived from 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rat. Monolayer cell cultures in multiwell plates are maintained in medium supplemented with hormones and fetal calf serum. Guided by a randomized table, drugs are administered to cultures singly or in combination. Thus far, we have defined dose-response curves for tamoxifen, adriamycin, thiotepa, and methotrexate. Of these agents, adriamycin consistently exhibits a greater cytocidal effect for a given concentration. When these agents are given in combination, a general enhancement of cytotoxicity is observed, although the effects are frequently not additive. Using this procedure, we have examined the drug sensitivity of cells from human tumor biopsies. Data are being compiled for retrospective comparison with the results of treatment for these patients. The procedure described is suitable for analysis of most solid tumors; the evaluation can be completed within 1-2 weeks. Ease of cell maintenance and the brief incubation required suggest that this system may be suitable for general clinical use.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008727:Methotrexate / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000627:therapeutic use
D000970:Antineoplastic Agents; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene; D004317:Doxorubicin; D008727:Methotrexate