The use of human cancer cell lines as a primary screening system for antineoplastic compounds.

Exponentially growing cells of human cancer lines have been utilized to investigate the cytotoxic activity of antineoplastic agents. Different cancer cell lines differ greatly in their responsiveness to both clinical and experimental cytotoxic drugs. For example, sensitivities to 5-fluorouracil and cytosine arabinoside ranged over 15- and 30-fold respectively. Cell lines derived from carcinomas were more sensitive to 5-fluorouracil and less sensitive to cytosine arabinoside than was a leukaemic cell line. In general, colon carcinoma lines were most resistant to DNA-intercalating drugs, and a breast carcinoma and leukaemia line most sensitive. In a congeneric series of amsacrine analogues, in vitro patterns of activity against different lines were shown to correlate with activity against the Lewis lung mouse carcinoma in vivo. Results suggest that established cell lines manifest responsiveness to anticancer drugs consistent with that expected from their tumours of origin. This assay is economical, reproducible and convenient, and could be used to complement the human tumour stem cell assay in drug development studies.