Explanation for side effect in people could provide way to avoid it
Heart damage from chemotherapy may be due to leaky pipes. Sunitinib, a cancer drug known to harm heart tissue, wipes out cells that seal blood vessels, Vishnu Chintalgattu of the biotech company Amgen and colleagues report May 29 in Science Translational Medicine.
These cells, called pericytes, normally wind around tiny blood vessels, or microvessels, keeping them healthy and plugging leaks like rubber patches glued to bicycle inner tubes.
Researchers examined tissue from drug-treated and untreated mice and noticed that sunitinib stripped pericytes from microvessels in the heart. Without the sheaths of sticky cells, more than twice as much fluid seeped from the microvessels.
Leaking liquid may explain why as many as 28 percent of sunitinib-treated cancer patients end up with heart trouble, the researchers suggest.
But there may be a way to fix the plumbing problem. Thalidomide, the molecule made famous for causing birth defects and now used to treat cancer, can protect pericytes from slaughter by sunitinib, the team reports.
Dosing lab-grown pericytes with only sunitinib killed the cells, but giving them both drugs didn’t seem to do any harm. And when researchers grafted human cancer tissue into mice and treated them with the two drugs, the animals’ tumors shrank and their hearts pumped normally.
V. Chintalgattu. Coronary microvascular pericytes are the cellular target of sunitinib malate-induced cardiotoxicity. Science Translational Medicine. Published online May 29, 2013. doi: 10.1126/scitranslmed.3005066. [Go to]