At least 3 patients brought me copies of the NYT article that appeared this week reviewing the prostate drug situation. As my faithful readers know, I have discussed all of these drugs many times in the past few years, since we have been pretty involved in their development and have put many patients at our clinic on them. A possible exception to this is XL184, or cabozantinib. The striking improvement in bone scans that is seen in the NYT article was first reported in a poster session last October, and I have been showing the same slide since then in my “prostate cancer talk” that I give to physicians and patient support groups. Cabozantinib is a drug that inhibits two signaling pathways, Met, and VEGFR2.
The met gene encodes a protein that is a receptor for hepatocyte growth factor. This alone should tell you that we have a lot to learn about various cancers and biology, since met has really not been high on the list of prostate cancer target genes. VEGFR2 is a receptor for vascular endothelial growth factor, a protein that normal tissues and cancer produce to stimulate blood vessel growth. Why blocking these two signaling pathways can produce such a striking and rapid change in bone scans is not clear to me, however it suggests that the effects may be on the cells in bone that take up the radioactive tracer as much as any effect on the cancer. However, since patients also experience drops in psa, improvement in bone pain, and delays in progression of disease, these two pathways must also play a crucial role in the bone/cancer interaction.
One hopes that the upcoming trials with cabozantinib will be another arrow in our quiver to fight prostate cancer. The side effects in trials to date have sometimes been challenging (severe fatigue, etc.) but there is a chance that lower doses might still produce benefit with fewer side effects. One of the biggest challenges of course, is how we will ever afford to be able to use all these new drugs in treating prostate cancer. Clearly the war will be difficult, since our society faces a daunting problem in controlling health care costs, and we better figure that out soon, or there won’t be a system left for discovering new drugs like this. By the way, the links in this article are all worth reading, but be sure to click on that last one.
And in the spirit of the weekend, happy 4th of July and God Bless America !