February 23, 2010 Leave a comment
After incorporating the realization that cancer biology was predicated on cell survival and not cell growth into our laboratory platform, we moved away from proliferative end points to cell death measures, and then redoubled our efforts to recreate the human tumor micro-environment in tissue culture. We immediately recognized that this required the preservation of cell-cell interactions found normally in the body as cellular clusters.
These cellular clusters better known as microspheroids, represent cohesive populations that interact directly with stroma, vasculature, inflammatory cells, and other tumor cells. Thus, the microspheroid recapitulates the human tumor environment. By applying cell death endpoints (the most rigorous of predictive measures) to these microspheroids, we have overcome most of the pitfalls encountered by earlier technologies. And, for the first time, a truly predictive human tumor model has been developed.
Of the two fundamental changes that we as a laboratory have brought to the field of chemosensitivity-resistance testing, the maintenance of cancerous tumor cells in their “native state” as microspheroids has been fundamental to our success.
Despite these important advances, many physicians have not grasped their significance. Falling back on their out-dated understanding of chemosensitivity studies that used growth-based endpoints (clonogenic, growth-to-confluence, and H3* thymidine incorporation, etc.) many physicians have failed to incorporate the use of these highly validated methodologies into their clinical practices.
A review of the published literature, correlating these more rigorous predictive methodologies with clinical outcomes, clearly establishes the validity of cell death in microspheroids as an important breakthrough in cancer treatment.