April 25, 2010 Leave a comment
At the recent meeting of the American Association for Cancer Research (AACR) held in Washington D.C (April 16-21, 2010), the theme remained consistent with the ground swell of interest in personalized care. Many of the sessions reflected the changing paradigm of clinical trials with a growing focus on biomarker analysis and patient selection predicated on genomic and proteomic features. Among the most compelling presentations were those that examined the manifest complexities of human signaling circuits. One presentation by Dr. Neal Rosen from Memorial Sloan Kettering in New York examined redundancy and feedback as principal determinants of clinical response to signal inhibitors. That session, chaired by Dr. Engleman from Harvard Medical School, examined the cross talk between EGFr and PI3K pathways. Using cell line systems, these investigators drilled down onto RNA and DNA expression profiles to examine how inhibitors acting for one pathway might up or down regulate parallel pathways.
This work dovetailed perfectly with our presentation on Monday, April 19, 2010 (Nagourney, R. et. al, Horizontal and vertical signal pathway inhibition in human tumor primary culture micro-spheroids. Abstract 1764, proceedings AACR 2010). In this analysis, we used small molecules tyrosine and serine/threonine kinase inhibitors to examine the points of commonality and disparity in these two crucial signaling pathways to assess how future drug combinations might provide response with these novel classes of agents.
The most exciting aspect of our work is the capacity of the human tumor micro-spheroid platform (EVA-PCD™) to capture all of the operative mechanisms of response and resistance. This, more closely than other platforms, recapitulates the complexity of human tumors and provides insight into these complex and redundant biological pathways. No genomic or proteomic tool can approximate the clinical relevance of the EVA-PCD™ platforms’ predictions.