Cytotoxic assays for screening anticancer agents.
In the process of identifying potential anticancer agents, the ability of a new agent is tested for cytotoxic activity against a panel of standard cancer cell lines. The National Cancer Institute (NCI) present the cytotoxic profile for each agent as a set of estimates of the dose required to inhibit the growth of each cell line. The NCI estimates are obtained from a linear interpolation method applied to the dose-response curves. In this paper non-linear fits are proposed as an alternative to interpolation. This is illustrated with data from two agents recently submitted to NCI for potential anticancer activity. Fitting of individual non-linear curves proved difficult, but a non-linear mixed model applied to the full set of cell lines overcame most of the problems. Two non-linear functional forms were fitted using random effect models by both maximum likelihood and a full Bayesian approach. Model-based toxicity estimates have some advantages over those obtained from interpolation. They provide standard errors for toxicity estimates and other derived quantities, allow model comparisons. Examples of each are illustrated.
Baharith
Lamya A
LA
Department of Statistics, King Abdul Aziz University, Jeddah, Saudi Arabia.
Al-Khouli
Abeer
A
Raab
Gillian M
GM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D017711:Nonlinear Dynamics
D000970:Antineoplastic Agents