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Is tumor calcification a good thing or a bad thing?
It's neither. It gives a much better understanding of what happens when Avastin is used. In pharmacology, the term agonist-antagonist is used to refer to a drug which exhibits some properties of an agonist (a substance that fully activates the neuronal receptor that it attaches to) and some properties of an antagonist (a substance that attaches to a receptor but does not activate it or if it displaces an agonist at that receptor it seemingly deactivates it thereby reversing the effect of the agonist).
When you culture endothelial cells with Avastin, all the VEGF gets pulled out of the culture medium and the endothelial cells undergo what is called "massive calcium accumulation death." Cytotoxic anticancer drugs antagonize the ability of Avastin to kill endothelial cells through this specific cell death mechanism. What is unique is that standard, traditional cytotoxic drugs inhibit Avastin, but the new "targeted" drugs don't inhibit it.
Clinical trials have shown that the combination of conventional chemotherapy with Avastin generally works better than either alone. But this is because Avastin has a very long half life (weeks) and it has the opportunity to work at times when the drug levels of the standard anticancer drugs go down to undetectable levels, where they won't antagonize the ability of low VEGF to cause death of the tumor endothelial cells. In other words, intermittent, "low dose" therapy might actually work much better than continuous "high dose" therapy.
In cell-based functional profiling assays, conducted on human tumor samples utilizing native microspheroids (fresh, live cells, not cell lines) replete with vascular, stromal and inflammatory cells to analyze cellular responses in the context of the tumor microenvironment, this snapshot of cellular response recapitulates patient response to cytotoxic compounds, signal transduction inhibitors and growth factor agonists/antagonists in real time.
Source: Cell Function Analysis
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Hybrid Mode
