Abstract
Advances in personalized medicine rely on knowledge of validated markers that predict response to treatment. The availability of such information could significantly impact preclinical drug optimization and reduce the cost of clinical trials. Conversely, improving drug efficacy based on clinical data requires performing studies in defined biological systems. These defined systems typically are clonal cell lines, which have been key in advancing our understanding of numerous disease states, including cancer. A number of recent comprehensive studies have demonstrated that individual cell lines are restricted along discreet lineages and therefore do not recapitulate tumor heterogeneity observed in patients However, the use of a combination of such cell lines reflected the clinical diversity observed in patient. (Neve et al, 2006; Kao J et al, 2006; Keller PJ et al 2010). We postulated that the use of carefully characterized cell lines combined into biologically relevant panels might provide valuable insights into studies on target validation, lead optimization, mechanisms of action and evaluation of efficacy in various patient subgroups. The lack of uniform culture conditions among various tumor cell lines hampers the design and conduct of experiments using such cell line panels and complicates the interpretation of the results obtained from them. We therefore undertook to combine panels of breast cancer cell lines that represented major clinical manifestations of the disease and culture them under standardized conditions. We were able to establish culture conditions that maintained the expression of mRNA and cell surface proteins for validated therapeutic and clinical markers. Using a small collection of clinically validated and investigational compounds we provide several example about how carefully selected and characterized cell panels can be used to carry out pharmacology studies and address questions pertinent to tumor biology and anti-cancer drug development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5268. doi:1538-7445.AM2012-5268