One Step Closer to Ending Cancer Pain

University of Toronto researchers have found a novel role for a cell membrane-anchored mediator in cancer pain. They suggest that the serine protease TMPRSS2-a gene previously shown to play a key role in some of the most aggressive forms of androgen-fuelled cancers-appears to be the trigger behind the most severe forms of cancer pain.

University of Toronto researchers have found a novel role for a cell membrane-anchored mediator in cancer pain, as well as pain in general. According to study results published in the May 2015 issue of Pain, the researchers suggest that the serine protease TMPRSS2—a gene previously shown to play a key role in some of the most aggressive forms of androgen-fuelled cancers—appears to be the trigger behind the most severe forms of cancer pain.

Led by David Lam, MD, DDS, PhD, FRCD(C), DABOMS, the Head and Assistant Professor in Oral and Maxillofacial Surgery at the University of Toronto, the research first focused on head and neck cancers, which have been shown to be the most painful; patients suffering head and neck cancer-related pain experience pain that is immediate and localized. Treatment options for these patients are limited to opioids.

When conducting research at the University of California San Francisco, Lam observed that the majority of head and neck cancer patients were men. This observation led him to investigate TMPRSS2 because of its known correlation with prostate cancer.

“Prostate cancer research already knows that if you have the TMPRSS2 gene marker, the prostate cancer is much more aggressive,” said Lam. “They've also shown that this is androgen (male hormone) sensitive.”

In the current study, Lam, who is also a consultant surgeon in dental oncology at the Princess Margaret Cancer Centre, the program lead and staff surgeon of the Oral & Maxillofacial Rehabilitation Program at Mount Sinai Hospital, and a staff clinician with the Wasser Pain Management Centre, discovered that TMPRSS2 was actually prevalent in much greater quantities in patients with head and neck cancers than in those with prostate cancer.

When TMPRSS2 comes into contact with the body’s nerve pain receptors, pain is triggered. Dr. Lam was able to determine that the more TMPRSS2 that came into contact with nerve pain receptors, the greater the pain was provoked.

When Lam and colleagues assessed various cancer types known to have pain associations, they found that the most painful cancers had cells with the highest levels of TMPRSS2. “It was exactly what we know clinically about pain association,” added Lam.

It is hoped that the new finding of the role played by TMPRSS2 in trigger cancer pain leads to the creation of targeted cancer pain therapies that work by inhibiting the expression of TMPRSS2 or its ability to affect pain receptors.

“The discovery that TMPRSS2 drives cancer pain demonstrates another way that cancers lead to suffering,” said co-author Brian Schmidt, DDS, MD, PhD, director of the Bluestone Center for Clinical Research and professor of Ooral and maxillofacial surgery at New York University College of Dentistry. “Inhibition of its activity in patients might provide a new form of treatment for cancer pain,” he added.

Adding to Schmidt’s thoughts, Lam explained that any “cancer that is painful before initiating drug treatment‑‑we can label the cancer cells for TMPRSS2 and look for this particular marker.” He also noted that targeting the production and expression of TMPRSS2 would be the most effective approach to ending pain.