A number of questions remain before scientists can assess the promise of this approach. Getting the pathway inhibitors themselves into the disorganized tumor vasculature might present a problem. Although this worked in the present study, the same might not always be the case in humans or in all tumors, says Ananth Annapragada, a researcher at the University of Texas, in Houston, who was not involved in the research. “Injecting the inhibitor systemically and hoping it will magically go to the right place might not work out,” he says. And the drugs might damage areas of the body where tissue remodeling is taking place, such as the liver he adds. “Having said that, the notion of enhancing tumor vascular permeability is very important and as soon as this paper comes out a lot of people will get to work on this to test it further and try and overcome such potential problems.”
An important next step, according to Coussens, would be to show that healthy tissues in the body would tolerate the leakier blood vessels. Although the mice used in the current experiments did not show any immediate ill effects of the treatment, they were not kept alive for long enough to discover longer-term side effects.
Because their intervention increased leakage even in already leaky tumor vessels, the researchers believe that the newly discovered pathway works independently of the mechanisms that normally make these vessels leaky. This is important because in many cases, the abnormal vasculature itself contributes to a tumor’s aggressiveness, as it improves nutrient supply to the tumor and permits cancerous cells to slip into the bloodstream and metastasize.
But although the present study did not asses the long-term effects on the tumors, Coussens says there is little reason to expect that blocking the pathway would make a cancer more aggressive: “Within a few hours of treatment the leakiness returns to normal, so we just open a transient window of opportunity for drug delivery. The hope would be that this should not be tumor-promoting, as the changes in blood vessels associated with metastasis happen in the much longer term.”