Tumour-penetrating molecule boosts cancer drug delivery
Researchers have identified a protein that can carry blood-borne drugs deep into tumours.
Writing in Science, University of California Santa Barbara scientist Kazuki Sugahara shows how a short protein molecule called iRGD can be used to enhance the uptake of drugs into cancers, permitting lower drug doses to be used and therefore reducing side effects.
A major problem with cancer therapies is that drugs delivered via the bloodstream often penetrate quite poorly into cancers; at best most make it about 4 cell-widths away from the delivering blood vessel. But the iRGD protein can crowbar its way through, covering millimetre distances which are orders of magnitude greater.
It targets tumours by first locking onto proteins called integrins, which are over-expressed in cancers. Within the tumour the protein is then cut in half, exposing a cancer-penetrating component that enables it to burrow away from blood vessels and into the body of the tumours, at the same time providing a portal of access for anti-cancer drugs.
The researchers found that when mice with tumours were given doses of iRGD together with the cancer drug paclitaxel, 12 fold more drug accumulated in the tumour than with paclitaxel alone. With another common cancer agent, doxorubicin, the concentration was 7 fold higher in the tumour when the agent was combined with iRGD. Tests also showed that the doses of the drugs could be reduced three fold and still achieve the same anticancer effects, but with far fewer systemic side effects.
The next step will be to assess the safety and efficacy of iRGD in humans. Encouragingly the integrin proteins targeted by iRGD are present in human cancers, suggesting that the system should translate into clinical practice.