[2014 World Pharma Congress] Phenotypic Screening of Compounds and Drug Combinations in BioMAP® Oncology Systems Reveals Divergent Effects on Clinically-relevant Biomarkers

[2014 World Pharma Congress] Phenotypic Screening of Compounds and Drug Combinations in BioMAP® Oncology Systems Reveals Divergent Effects on Clinically-relevant Biomarkers
Version:
051914

File Name/Number:
2014 World Pharma Congress

Year:
2014

The tumor microenvironment consists of a complex array of interacting players including hyperproliferative malignant epithelial cells, stromal fi broblasts, activated vasculature, as well as polarized and suppressed immune cells. Understanding how drugs impact both cancer cells as well as the cells of the host microenvironment has prompted renewed efforts to develop more robust and physiologically relevant in vitro models. For the past decade, BioSeek’s proprietary BioMAP® technology platform has helped bridge the gap between in vitro and in vivo testing by correlating drug effects in primary human cell-based assays to clinically relevant results.

We show that the primary tumor type as well as the host microenvironment signifi cantly influences the effects of compounds on clinically relevant biomarkers, refl ecting the involvement of cues provided by cell-cell and cell-matrix interactions in these oncology models. For example, paclitaxel exhibits immune-enhancing effects with increased GranzymeB, TNF alpha, and IFN gamma levels in StroHT29 and VascHT29 colon adenocarcinoma model systems. In contrast, in the non-small cell lung cancer systems, StroNSCLC and VascNSCLC, the profi le of paclitaxel isconsistent with immune inhibition and decreased TH1-type cytokines. We also compared the profi les of drugs tested alone and in combination in these BioMAP oncology systems. Specifi cally, enhanced activities were detected with the combination of Dabrafenib, a BRAF inhibitor, and Trametinib, a MEK inhibitor, compared to effects of the individual agents. These new oncology BioMAP systems provide human physiological and pharmacological information on how drugs, as monotherapies or combinations, impact the biology of cancer-host cell interactions.