Title:Guide for Selection of Relevant Cell Lines During the Evaluation of new Anti-Cancer Compounds
Volume: 18
Issue: 8
Author(s): Angel J. Ruiz-Moreno, Patricia Torres-Barrera, Mireya Velázquez-Paniagua, Alexander Dömling and Marco A. Velasco-Velázquez*
Affiliation:
- Departamento de Farmacologia, Facultad de Medicina, Universidad Nacional Autonoma de Mexico (UNAM), Ciudad de Mexico,Mexico
Keywords:
Anti-cancer drugs, preclinical screening, cancer cell line, NCI-60, EGFR, CD44, cancer genomics.
Abstract: Background: Human cancer cell lines are valuable models for anti-cancer drug development.
Although all cancer cells share common biological features, each cancer cell line has unique genotypic/ phenotypic
characteristics that affect drug response. Thus, the information obtained with a specific cancer cell line cannot
be easily extrapolated to other cancer cells. Consequently, cell line selection during experimental design is
critical for providing proper and clinically relevant structure-activity analysis.
Methods: Herein, we critically review the use of cancer cell lines as tools for activity analysis by comparing two
different scenarios: i) the use of multiple cancer cell lines, with the NCI-60 Program as the most representative
example; and, ii) the selection of a single cell line with specific biological characteristics that match the rationale
of compound design.
Results: Considering that most laboratories evaluate the activity of new compounds using few cell lines, we
provide a systematic strategy for selection based on the expression levels and genetic status of the target and the
effectiveness of target inhibition or silencing. We exemplify the use of public databases for data retrieval and
analysis as well as the critical comparison of such information with published results.
Conclusion: This approach refines cell line selection, avoiding the perpetuation of published poor selection and
enhancing the relevance of the results.
