Medications used to alleviate common conditions sometimes give us pleasant surprises when it is found that they also have properties that can be very useful in combating serious diseases. That is what has now happened with lidocaine, an anesthetic that a new study has shown has the ability to kill cancer cells.
It had already been suggested that this local anesthetic had beneficial effects in cancer patients, but it was not known how or why. Now, a team of researchers at the Perelman School of Medicine at the University of Pennsylvania has discovered that Lidocaine-ofad – commonly used as an anesthetic in outpatient medical procedures – activates certain bitter taste receptors through two unique mechanisms that resulting in the death of cancer cells.
The team found that lidocaine activates the bitter taste receptor T2R14, which is elevated in several cancer cells. When this receptor is activated, a process called apoptosis begins, which causes the death of cancer cells. The specific mechanisms that allow lidocaine to activate T2R14 are mitochondrial calcium ion overload, which produces reactive oxygen species that can damage biomolecules, and proteasome inhibition, which together cause cell death.
Improved survival in patients with head and neck cancer
Previous work the researchers carried out showed that bitter taste receptors are found on many cancer cells in the mouth and throat, where they trigger apoptosis, and that increasing the expression of these bitter receptors is associated with better survival outcomes in patients with head and neck cancer. In April 2023, a clinical trial published in the Journal of Clinical Oncology revealed that breast cancer survival increased when lidocaine was administered before surgery.
“We have been following this line of research for years, but were surprised to discover that lidocaine targets the receptor that is most highly expressed in all cancers,” said Robert Lee, assistant professor of Otolaryngology-Head & Neck Surgery, who has led the work. “T2R14 is found in cells throughout the body. “What’s incredibly exciting is that there are many drugs that activate it, so there could be additional opportunities to think about repurposing other drugs that could safely target this receptor.”
“While we are not suggesting that lidocaine can cure cancer, we are excited by the possibility that it could gain an advantage in the treatment of head and neck cancer.”
T2R14 helps us perceive a bitter taste in the mouth, but the receptor’s function in other cells in the body is unclear. Lidocaine is usually injected into the skin or other tissues to prevent pain by blocking nerve signals and could easily be injected directly near or around accessible oral tumors.
“As a head and neck surgeon, we use lidocaine all the time,” explained Dr. Ryan Carey, who is also an assistant professor at the same center and the other director of the study. “We know lidocaine is safe, we feel comfortable using it, and it is available, meaning it could be seamlessly incorporated into other aspects of head and neck cancer care.”
The study, which was done primarily on head and neck squamous cell carcinoma cell lines, also found that T2R14 is particularly elevated in these types of tumors associated with human papillomavirus (HPV), which is now the dominant form. of squamous cell carcinoma of the head and neck.
Carey is planning a clinical trial at Penn Medicine’s Abramson Cancer Center to test the addition of lidocaine to standard treatment for HPV-associated head and neck squamous cell carcinomas. “While we are not suggesting that lidocaine can cure cancer, we are excited by the possibility that it could gain an advantage in the treatment of head and neck cancer and make progress in terms of improving treatment options for patients with this form.” challenging cancer,” concludes the researcher.
