Researchers tested a new glowing dye called pafolacianine that was designed to help surgeons see cancer cells during operations. The dye works well for ovarian cancer, but this study found it doesn’t work effectively for head and neck cancers. Scientists tested the dye in cancer cells, in mice with tumors, and in human tissue samples. They discovered that head and neck cancer cells don’t have enough of the target protein that the dye needs to attach to, so the dye couldn’t light up the cancer during surgery. This negative result is actually important because it prevents doctors from wasting time and resources on a treatment that won’t help patients.

The Quick Take

  • What they studied: Whether a new glowing dye (pafolacianine) could help surgeons see and remove head and neck cancer more completely during surgery
  • Who participated: Laboratory cancer cells, mice with human cancer tumors implanted in them, and 16 human tissue samples (8 from tumors and 8 from normal tissue)
  • Key finding: The glowing dye barely lit up head and neck cancer cells and tumors, performing much worse than expected. The dye only glowed at about one-quarter the brightness of a similar dye that actually works well for this purpose
  • What it means for you: This dye won’t be useful for head and neck cancer surgery. However, this research helps doctors avoid pursuing ineffective treatments and encourages them to develop better alternatives. If you’re facing head and neck cancer surgery, your surgeon will continue using current methods for finding cancer edges during surgery

The Research Details

This was a laboratory and animal study designed to test whether pafolacianine could work for head and neck cancer surgery. The researchers started with cancer cells grown in dishes, testing whether the glowing dye would stick to them. They then moved to mice that had human head and neck cancer tumors growing inside them, injecting the dye and watching whether it lit up the tumors. Finally, they examined actual human tissue samples from patients to see if cancer cells had the protein target that the dye needs to attach to.

The study used two different types of head and neck cancer cells (FaDu and UMSCC47) and tested the dye at different concentrations to see if higher amounts would help. They also compared pafolacianine to another glowing dye called panitumumab-IRDye800CW, which is known to work well for this type of cancer, to have a reference point for what success should look like.

The researchers used a technique called immunohistochemistry, which is a way to stain tissue samples so you can see specific proteins under a microscope. This allowed them to measure how much of the target protein (folate receptor-alpha) was present in cancer versus normal tissue.

This research approach is important because it follows the proper steps before testing a new drug in patients. By thoroughly testing in cells and animals first, researchers can identify problems early and avoid exposing patients to treatments that won’t work. The comparison to a successful alternative dye helps show that the problem isn’t with the testing method itself, but with pafolacianine specifically.

This study has several strengths: it used multiple cancer cell types, tested in both laboratory and living animal models, and examined actual human tissue. The researchers included a positive control (the working dye) to verify their methods were sound. However, the human tissue sample size was small (only 16 samples total), and the study was conducted in laboratory settings rather than in actual patients. The findings are clear and consistent across all three testing levels, which increases confidence in the results.

What the Results Show

The glowing dye pafolacianine performed poorly across all three testing levels. In cancer cells grown in dishes, the dye barely attached to the cells, showing fluorescence levels similar to or even lower than control cells that shouldn’t have the target protein at all. When the dye was injected into mice with head and neck cancer tumors, it failed to concentrate in the tumors. Instead, the dye spread throughout the body and actually glowed more brightly in normal skin tissue than in the cancer itself—the opposite of what you want for surgery guidance.

The brightness measurements tell the story clearly: pafolacianine produced a fluorescence intensity of only 7.39 in one cancer type and 6.97 in another. In comparison, the working dye (panitumumab-IRDye800CW) produced intensities of 32.14 and 14.98 in the same cancer types. This means the working dye was roughly 4-5 times brighter in the tumors than pafolacianine.

When researchers examined human tissue samples, they discovered why the dye wasn’t working: head and neck cancer cells don’t have significantly more of the target protein (folate receptor-alpha) than normal tissue does. The dye is designed to find and attach to this specific protein, but if the protein isn’t there in high amounts, the dye has nothing to grab onto. This fundamental mismatch explains all the negative results.

The study revealed that pafolacianine distributed throughout the body rather than concentrating in tumors, which could be a safety concern if used in patients. The dye showed no advantage over background tissue, meaning surgeons wouldn’t be able to distinguish cancer from healthy tissue during an operation. The comparison to panitumumab-IRDye800CW demonstrated that the testing methods themselves were valid and sensitive enough to detect good tumor targeting—the problem was specific to pafolacianine and head and neck cancer.

Pafolacianine was previously approved by the FDA and shown to work well for ovarian cancer surgery because ovarian cancer cells express high levels of the folate receptor-alpha protein. This study shows that head and neck cancers are fundamentally different—they don’t have this protein in sufficient quantities. This highlights an important principle in precision medicine: just because a treatment works for one cancer type doesn’t mean it will work for another. The field has other fluorescence-guided surgery agents in development that target different proteins found on head and neck cancers, and those may prove more effective.

The human tissue samples were limited to only 8 tumor and 8 normal samples, which is a small number for drawing firm conclusions about all head and neck cancers. The study used cancer cells and mice with implanted human tumors, which don’t perfectly replicate how cancer behaves in actual patients. The researchers didn’t test pafolacianine in living patients, so they can’t be completely certain how it would perform in a real surgical setting, though the consistent negative results across all three testing levels make this unlikely. Additionally, the study focused on one specific type of head and neck cancer protein target and didn’t explore whether pafolacianine might work better for specific subtypes of head and neck cancer.

The Bottom Line

Based on this research, pafolacianine should not be pursued for head and neck cancer surgery (high confidence). Surgeons and researchers should focus on developing or using alternative fluorescence-guided surgery agents that target proteins actually present on head and neck cancers (high confidence). For patients with head and neck cancer, current surgical techniques for identifying cancer margins remain the standard approach (high confidence).

Head and neck cancer surgeons and patients should know that pafolacianine won’t be a useful tool for their operations. Researchers developing new cancer surgery techniques should learn from this that target protein expression must be validated before investing in clinical trials. Pharmaceutical companies should understand the importance of testing new agents across different cancer types rather than assuming success will transfer. Patients considering participation in clinical trials for new cancer treatments should feel reassured that negative studies like this help prevent them from being exposed to ineffective treatments.

This is a negative study, so there is no timeline for patient benefits. Instead, the benefit is immediate: preventing wasted resources and protecting patients from ineffective treatment. Researchers can now redirect efforts toward alternative approaches that may actually work for head and neck cancer.

Want to Apply This Research?

  • If you’re a head and neck cancer patient or survivor, track your surgical outcomes and follow-up imaging results in your health app to monitor for cancer recurrence. Note the date of your surgery and any imaging follow-ups (CT, MRI, PET scans) to maintain a clear timeline of your treatment journey.
  • Stay informed about your cancer treatment options by discussing with your surgical team what imaging and guidance methods they use during your procedure. Ask your doctor which proven techniques they’ll use to ensure complete cancer removal. Keep a record of all your appointments and treatment discussions in your health app.
  • For long-term monitoring, track any new symptoms or concerns between appointments, document follow-up imaging results and dates, and maintain a list of questions for your oncology team. Use your app to set reminders for scheduled follow-up appointments and imaging studies, which are crucial for detecting any cancer recurrence early.

This research describes laboratory and animal studies, not human clinical trials. The findings suggest pafolacianine is not effective for head and neck cancer surgery, but this does not affect current treatment options available to patients. If you have head and neck cancer or are at risk, consult with your oncologist or head and neck surgeon about the most appropriate treatment and surgical guidance methods for your specific situation. This article is for educational purposes and should not replace professional medical advice. Always discuss new or experimental treatments with your healthcare provider before considering them as options.