Scientists have just discovered that brain tumors can grow their own blood vessels – revealing why drugs designed to choke off their blood supply often fail to extend the lives of cancer patients.
About 40 years ago, a Harvard biologist suggested that – since tumors are dependent on surrounding blood vessels to nourish them – stifling the blood supply would kill the cancer. Approved in 2004, Avastin from Genentech/Roche was the first drug to inhibit angiogenesis – the process of growing new blood vessels to supply nutrients and oxygen and remove waste. But this highly anticipated drug, along with others that followed, proved disappointing.
And that's because scientists have always thought that the tumor's new network of blood vessels sprouted from pre-existing capillaries in the brain. But two new, independent studies published in Nature on Sunday have discovered blood vessels grown directly from cancer cells.
Both studies examined tumor samples from patients with glioblastoma, one of the most aggressive human cancers and supplied by extensive networks of abnormal vessels. The researchers found that some of the cells that line the blood vessels in the glioblastoma carry the same genetic signatures as the tumor cells. That is, those blood-vessel cells are of tumor origins.
Some tumor cells have qualities of stem cells, which are famous for being able to renew themselves and differentiate into various other kinds of cells. The researchers found that these tumor stem-like cells go on to become tumors as well as the blood vessels that feed them.
The New York study, led by Viviane Tabar from the Memorial Sloan Kettering Cancer Center, took some of these stem-like cells, injected them into mice, and examined the mouse tumors. A large percentage of the blood vessels that developed in the tumors were of human, not mouse, origin, indicating that they were derived directly from the tumors themselves.
"We were able to identify blood vessels of human origins in the brains of mice carrying the tumors," Tabar said.
The Italian study led by Ruggero De Maria from Istituto Superiore di Sanità in Rome and Roberto Pallini from Catholic University of Rome found that 20 to 90% of the blood vessels were tumor-derived. Then they killed the tumor-derived blood-vessel cells, which caused the tumors to shrink, showing their reliance on those blood vessels.
The bottom line: "There is plasticity within the tumor, and it can make its own blood vessels," Tabar said.
New anti-cancer therapies will require a drug duplex: one to kill the normal blood vessels that have gone astray and another to kill the tumor-begotten ones.
Image: Gliobastoma by Christaras A under Wikimedia Commons