Researchers have discovered that some cancer cells can draw blood from existing mature blood vessels allowing them to continue to spread. These findings are published in the journal Nature Medicine.
Cancers are often managed by surgical removal of the tumor. However, as many as half the patients who undergo this procedure to treat colon cancer will develop liver metastasis. Metastasis occurs when cancer cells break away from the primary tumor site and enter the bloodstream, spreading to other parts of the body. It is usually this recurrence of cancer that is fatal for patients.
In an attempt to stop metastatic growth, scientists have focused on angiogenesis—a well-known mechanism by which cancer cells generate new blood vessels in order to grow. In the last decade, researchers have developed drugs to target this process.
It seemed obvious that if you block the ability of the tumor to obtain blood—its oxygen and nutrients - you would be able to slow the tumor growth, if not kill it completely. Surprisingly, these drugs, called anti-angiogenic treatments, have succeeded in slowing the growth of some cancers, but they have not successfully increased patient survival.
"We were treating all patients as if they were generating new blood vessels, but our research has revealed that roughly 40-45 per cent of tumors derive their blood supplies from new blood vessels, and another 40-45 per cent derive their blood supplies by co-opting existing blood vessels of the liver to draw their blood, which explains why existing therapies that target new blood vessels are not working as well as predicted," says the lead author. "We thought tumors always generated the growth of new blood vessels but in some cases what they are doing is a little sneakier: the cancer cells surround the existing blood vessels of the liver to draw their blood supply. We need to select our patients based on how their cancers obtain their blood supply and stratify them for the right treatment, essentially personalizing medicine."
Authors found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone.
Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy.