New cancer drugs linked to side effect issues

Angiogenesis inhibitors that block a tumor’s development of an independent blood supply have been touted as effective cancer fighters that result in fewer side effects than traditional chemotherapy. However, a new study by researchers at UCLA’s Jonsson Cancer Center showed that one method of blocking blood supply development could result in serious and potentially deadly side effects.

Several newly developed angiogenesis inhibitors work by blocking vascular endothelial growth factor (VEGF), an important signaling protein that spurs growth of new blood vessels. Genentech’s Avastin, an approved angiogenesis inhibitor for colon and lung cancers, inhibits angiogenesis by blocking VEGF signaling from outside of the cell.

UCLA researchers wanted to know what happened when VEGF signaling was blocked from within endothelial cells, a mechanism used by some small molecule drugs currently being tested in late phase clinical trials. However, more than half of the mice in the study suffered heart attacks and fatal strokes, while those that remained alive developed serious systemic vascular illness.

Luisa Iruela-Arispe, a professor of molecular, cell and developmental biology and director of the Cancer Cell Biology program at UCLA’s Jonsson Cancer Center, said: “This was an extremely surprising result. I think this study is cause for some caution in the use of angiogenesis inhibitors in patients for very long periods of time and in particular for use of those inhibitors that block VEGF signaling from inside the cell.”

About 5% of patients taking Avastin develop blood clot-related side effects, Professor Iruela-Arispe said. But because Avastin was approved only three years ago, it is unclear what side effects may occur when patients remain on the drug for many years, she added.