Lidocaine, often used as numbing agent for outpatient medical procedures, activates certain bitter taste receptors through two unique mechanisms that result in cancer cell death, according to researchers from the Perelman School of Medicine. Their findings, published in Cell Reports, pave the way for a clinical trial to test the addition of lidocaine to the standard of care therapy for patients with head and neck cancers. The local anesthetic drug has long been suggested to have beneficial effects in cancer patients, but it wasn’t known how or why.
The preclinical study is led by Robert Lee and Ryan Carey, both assistant professors of Otorhinolaryngology—Head & Neck Surgery, and Zoey Miller, a pharmacology graduate student at Penn and member of Lee’s lab. The team found that lidocaine activates the bitter taste receptor T2R14, which is elevated in various cancer cells. When this receptor is activated, it starts a process called apoptosis, causing the cancer cells to die. 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, together resulting in cell death.
Previous work by the team showed that bitter taste receptors are found in many oral and throat cancer cells, where they trigger apoptosis, and that increased expression of these bitter receptors is correlated with improved survival outcomes in patients with head and neck cancer. In April 2023, a multi-institutional randomized clinical trial published in the Journal of Clinical Oncology found that breast cancer survival increased when lidocaine was administered before surgery.
“We’ve been following this line of research for years but were surprised to find that lidocaine targets the one receptor that happened to be most highly expressed across cancers,” Lee says. “T2R14 is found in cells throughout the body. What’s incredibly exciting is that a lot of existing drugs that activate it, so there could be additional opportunities to think about repurposing other drugs that could safely target this receptor.”
Read more at Penn Medicine News.
