New Pharmaceutical Technology Developed at NC State Holds Promise for Treating Common Cancer in Horses

Horses are happiest when soaking up the sun outdoors, but long-term exposure to harmful UV rays without protection leads many horses to develop skin cancer.

Squamous cell carcinoma, or SCC, is the second most common type of cancer in horses and frequently develops in unpigmented areas around and on the eye, where treatment can be tricky. 

For several years, the gold standard of eyelid SCC treatment was photodynamic therapy aided by a drug called verteporfin, says Dr. Annie Oh, an assistant professor of ophthalmology at the NC State College of Veterinary Medicine.

Then the COVID-19 pandemic hit and verteporfin was in short supply, causing veterinarians to turn to other therapies. Paclitaxel, a chemotherapeutic drug used in humans with SCC, could treat equine SCC but was quickly processed by tumor and surrounding tissue.

Dr. Yevgeny Brudno, an associate professor within NC State and UNC-Chapel Hill’s Lampe Joint Department of Biomedical Engineering, and Dr. Callie Fogle, an NC State clinical professor of equine surgery, reached out to Oh with an idea: A pharmaceutical technology Brudno developed, called Tissue Reactive Anchoring Pharmaceuticals (TRAPs), could prolong paclitaxel’s effectiveness in treating these tumors. After participating in a preliminary study using a mouse model, Oh launched a corresponding equine clinical trial last April.

Oh’s equine pilot study has shown that the combined TRAPs-paclitaxel treatment shows incredible promise in treating horses with eyelid SCC, with most horses showing complete or partial resolution of the disease post-treatment. As she organizes a subsequent study to optimize drug concentration and dose, Oh shares how this technology could change the landscape of SCC treatment in horses — and potentially humans, too.

What motivated you to take a closer look at equine squamous cell carcinoma?

Dr. Annie Oh: One of the most frustrating things I experienced as a resident was when I didn’t have any more options. That really bothered me with cases, having to say, “This is all I have to offer.” That’s why I like research, to find other options when there’s nothing else available.

I’ve seen ocular SCC a lot in horses at NC State, during my residency and now. About 40 to 50% of all equine squamous cell carcinoma cases affect the eye — that’s a large percentage. It affects all types of horses. There’s a really big need for treatment.

With the Visudyne [the brand name for verteporfin] shortage during the pandemic, we went back to, in my opinion, the Dark Ages for SCC treatment. So when Dr. Brudno and Dr. Fogle came to me with this idea, I thought it was something new we could try. NC State has a particularly heavy investment in equine ophthalmology.

How could this treatment help horses and their owners?

AO: A benefit of the TRAPs technology is that right now it’s linked to paclitaxel, but you can actually change out that drug if you wanted to and use it with other medications. The other thing is that you can inject it in its liquid form, so you can do this procedure in a standing horse. You don’t have to put the horse under general anesthesia — that’s a big plus.

Another plus is that it’s inexpensive to make. So to me, I felt like if I could get treatment that was easy to give and affordable to make, so it didn’t cost too much to be able to treat more horses and treat them earlier, that was a better deal.

With squamous cell carcinoma, you have to continuously look out for horses developing new spots. If this therapy works out the way I envision it, horses don’t always have to come to us for treatment. They can actually get treated by general practitioners, so it increases accessibility.

How do TRAPs work?

AO: The main concept is that it’s a local depot that keeps the drug there longer. It’s an injectable liquid that’s created using a two-step process synthesis, so it doesn’t take much to make.

Essentially, there’s what’s called an anchoring motif, in this case an NHS [N-hydroxysuccinimide] protein, connected to a linker, which connects to the drug. So the thought is that this anchoring motif will anchor to tumors, specifically their extracellular matrix, and then over time these linkers will dissolve and release the drug.

A lot of current materials used to keep drugs in locations longer — they’re called excipient materials — use some kind of viscous oils or micro-sized particles. But with this new technology, you don’t need any of that. Because it’s so liquid and easy to inject, you can also inject it into really stiff tumors.

This work is translational from human to animal medicine, by taking a chemotherapeutic treatment used for SCC in humans and giving it to horses. Could your findings about TRAPs’ efficacy in horses translate back into use in human therapies?

AO: Horses are a naturally occurring animal model for squamous cell carcinoma in humans, and TRAPs aren’t used in humans yet. Humans are really good about treating our skin cancers, but I think this therapy still could have a role in cancer treatment.

In general, multimodal cancer therapy is the best approach — trying different things, particularly if you have a recurrence. What TRAPs’ role will play in cancer treatment will depend on what human physicians think, but at least in horses it does shrink the tumor in size and is easy to give in hard places. 

It’s important to have accessibility in health care. On the human side, too, treating and detecting cancer sooner is always better, and so having a treatment option that’s cheap and potentially deliverable via mobile clinics, this might be an option. It comes down to whether human oncologists find an area where TRAPs could be helpful for them.

[Note: Brudno’s research showed the TRAPs technology was effective at creating drug depots in resected human pancreatic tumor tissues, but further research is needed.]

How can people prevent their horses from developing squamous cell carcinoma?

AO: Sunscreen, UV fly masks, keeping them out at night and in during the day. Inspecting the horses often for squamous cell lesions and getting them treated early is vital. Look for growths with irregular boundaries or ulcerated areas, or anything pink and proliferative.

This conversation has been edited and condensed for clarity.

Dr. Oh would like to credit additional team members for their research assistance: Graduate research technician Rukesh Chinthapatla, ophthalmology resident Dr. Emi Retter and veterinary pharmacist Dr. Dan Aber.