Chemotherapy drugs may be effective at killing tumours, but that’s not all they attack in their journey through the bloodstream. The amount of these cancer-fighting medicines that can be administered to patients is therefore limited by their potentially fatal side effects.
It’s a problem that US researchers hope to tackle with a new device designed to absorb the excess drug that isn’t being used to attack the tumour and that would normally circulate around the body. And while ‘ChemoFilter’ is still in the very early stages of development, it’s already showing huge promise for improving the effectiveness and reducing the toxicity of chemotherapy treatment.
The device was originally conceived by interventional neuroradiologist Steven Hetts, an associate professor of radiology at the University of California San Francisco (UCSF). Hetts specialises in treating eye tumours in infants by navigating a catheter from the femoral artery in the thigh to the ophthalmic artery that supplies blood to the affected eye and pumping chemotherapy medications through the tube to the tumour.
“About half the drug will pass through the eyeball and get pumped around the body, giving the kids side effects. So it occurred to me that maybe we could put a device in the veins that are draining the organ to remove that excess chemotherapy before it can get pumped all over the body,” he recalls.
The eye cancers that Hetts specialises in, however, are rare, so he and his team initially decided to work on a device to improve the treatment for liver cancer, the third-leading cause of cancer deaths globally, with an estimated half a million new cases each year. It’s a disease that’s treated in a similar way to eye tumours, but the drugs are administered via the hepatic artery and drained via the hepatic vein.
The breakthrough came when Hetts’ trainee Anand Patel reached out to the materials sciences division at the University of California Berkeley. “I received an email saying the team at UCSF needed some help with material science, which I passed on to my group and an hour or two later, one of my post doc students Chelsea Chen came running to my door all excited, saying the polymer membranes she was working on for fuel cells could work for this device,” remembers Nitash Balsara, a chemical engineering professor at UC Berkeley and lead-PI of the Soft Matter Electron Microscopy program in Berkeley Lab's Materials Sciences Division.
She was right. Hetts’ proposed drug-capture device could benefit from the property in the fuel cell material, which allows it to attract and capture certain molecules by their electric charge while allowing other types of molecules to flow through. Specifically, a popular chemotherapy drug called doxorubicin – which is used to treat liver cancer – has a positive charge, so if a device using the material was inserted in the right place in the patient’s system, it could attract and absorb the excess drug molecules that weren’t fighting the tumour.
After investigating further, the team came up with the first version of ChemoFilter. “It’s basically a closed umbrella, which is inserted in the vein coming out of the liver, and can then be opened up to absorb the excess drug,” explains Balsara. The team’s lab experiments on pigs showed that it is able to absorb 90% of the drug in 25 to 30 minutes. Without the device, around half of the drug that is administered to kill the tumour would go straight to the heart, causing significant damage.
While the results of the team’s initial experiments with the ChemoFilter device are extremely encouraging, it’s still early days, according to Balsara. “All of the work up until now was done with no explicit funding – we were just trying things out. What this result means is that we now have a four-year grant to systematically explore all aspects of the project – what should the umbrella look like? How many umbrellas would we need? Should it be an umbrella or something else? What should the material that absorbs the drug look like?” he says.
He’s optimistic – if realistic – about how soon this innovation could be brought to patients. “The grant has no human component, but my suspicion is that once the animal experiments have been proven and we have more details on what kind of umbrella has to be made, there will be a lot of support, maybe even commercial support, to move the project forward quickly,” he predicts. “I think a three to four year timeframe is realistic. Of course, we’re prepared for roadblocks along the way.”
Looking at the practical side of things, Hetts is keen to stress that, while the use of this device would mark a step change in chemotherapy treatment, the basic surgical techniques needed to insert the device already exist. “What’s nice is that there are people very much like me – interventional radiologists – who do what I do but they do it from the neck down instead of in the brain and they’re very familiar with operating in this location,” he explains. “The ChemoFilter device would probably be quite similar in its geometry and how you would deploy it to other devices they’re used to using.”
There’s also potential to create devices that would work for other cancers in the future. “It’s a generally applicable concept, so you could pair any drug with a ChemoFilter that’s designed to bind up that particular drug,” Hetts remarks.
Balsara agrees. “The basic concept is very general and very powerful and could certainly affect chemotherapy down the road,” he concludes. “Right now, the amount of drug you inject is limited by how much damage it does. But if you reduce the toxicity, you can inject more of the drug. There is hope that devices like this could increase the efficacy of treatment for many kinds of tumours.”