Analysis of chemotherapeutic response heterogeneity and drug clustering based on mechanism of action using an in vitro assay.

摘要

BACKGROUND: Cancer chemotherapeutic treatment is a complex scientific task. The ChemoFx Drug Response Marker (DRM) assists physicians in identifying treatment protocols likely to be effective for specific patients. MATERIALS AND METHODS: The ChemoFx DRM was used to study drug response in vitro. Established human cancer cell lines and primary cultures of patient tumor specimens were challenged with chemotherapeutic agents to observe response of multiple tumor samples and determine whether drugs with similar mechanisms of action elicit similar response. RESULTS: These studies demonstrated heterogeneous response among patient tumor samples and clustering of drug response with similar mechanisms of action. Also highlighted was the reproducibility of ChemoFx DRM and its utility in characterizing tumor response to chemotherapy. CONCLUSION: Heterogeneous drug responses observed in vitro were similar to those observed clinically. Response characteristics were similar for drugs with similar mechanisms of action, suggesting response heterogeneity is determined at a cellular and molecular level.