This is one of the most important papers of the year. They look at the mechanisms of action of Optune and come up with ideas to improve the effectiveness of Optune. My favorite is where they talk about 5-ala. 5 ala is a dye, approved as Gleolan to be used during brain tumor surgery to help the surgeon tell the difference between tumor and normal brain. The dye accumulates in tumor only. Optune increased the concentration of the dye in the tumor but not in the normal brain, so to start with - combining Optune and Gleolan for a surgery would seem helpful. However, there are new clinical trials going on now where 5-ala is used in a new way called sonodynamic therapy. They give the 5-ala then wait for the tumor to take up the dye, then they treat the tumor noninvasively with focused ultrasound. The focused ultrasound excites the dye causing it to kill the tumor cells. Too early to tell how good it is by itself but imagine the possibility of easily increasing it's effectiveness just by using Optune while waiting for the dye to be taken up by the tumor? They also talk about Optune opening the blood brain barrier letting chemotherapies in that couldn't pass the blood brain barrier by themselves. This opens up a lot of possibilities. They also talk about the immune effects - possibly adding a checkpoint inhibitor may help with that. They talk about the effect Optune has on migration and movement of cancer cells. It slows them down. The problem we have with drugs like Avastin is they cut off the blood supply to the tumor, which causes the tumor cells to migrate towards a better oxygen supply. Imagine if we add Optune - to stop that migration. Perhaps the combination (which is being tested now in trials) could be a home run by starving the tumor cells and stopping them from invading the normal brain.
The best part of all of this is that all of the components are FDA approved and could possibly be used off label. Our patient navigation program is probably the best way to screen all of the possibilities!
The mechanisms of action of Tumor Treating Fields