A new study has uncovered how the commonly used local anesthetic drug, lidocaine, activates bitter taste receptors to exert an anti-cancer effect in head and neck cancers. Given its low cost and ready availability, the drug could easily be incorporated into the treatment of patients with this challenging form of cancer.
Researchers at the University of Pennsylvania School of Medicine have discovered that lidocaine targets a specific receptor, known as T2R14, which is highly expressed in head and neck squamous cell carcinomas (HNSCCs). These cancers have a high mortality rate and can cause significant treatment-related morbidity.
Bitter taste receptors, including T2R14, are involved in various biological processes, such as innate immunity and thyroid function. Previous studies have shown that T2Rs trigger apoptosis or programmed cell death in oral and throat cancers. Additionally, increased expression of T2Rs has been associated with improved survival outcomes in patients with HNSCCs.
The researchers found that lidocaine activates the T2R14 receptor in HNSCCs, leading to apoptosis of the cancer cells. This activation causes mitochondrial calcium overload and disrupts the mitochondrial membrane, significantly reducing the viability of HNSCC cells. Lidocaine also triggers the production of reactive oxygen species (ROS), indicating mitochondrial dysfunction and cellular stress.
Furthermore, the study suggests that lidocaine inhibits proteasomal degradation—a process that eliminates damaged or obsolete proteins from cells. When proteasomal activity is inhibited, proteins accumulate and can induce apoptosis. Lidocaine-induced proteasome inhibition was reversed when either ROS generation or T2R14 signaling was inhibited, indicating that proteasome inhibition resulted from T2R stimulation, mitochondrial dysfunction, and ROS.
One advantage of using lidocaine as a potential treatment for HNSCCs is that the affected sites are easily accessible, allowing for the implementation of the drug as an injectable or topical anticancer treatment.
The research also revealed that T2R14 is particularly elevated in HNSCCs associated with human papillomavirus (HPV), which is now the dominant form of HNSCC. Therefore, a clinical trial is planned to test the addition of lidocaine to standard care for HPV-associated HNSCCs.
While the researchers clarify that lidocaine cannot cure cancer, they are optimistic about its potential to improve treatment options for patients with head and neck cancer. Lidocaine’s safety, widespread availability, and low cost make it a promising candidate for further exploration in the field of cancer treatment.
The findings open up possibilities for the repurposing of other drugs that activate T2R14, which could offer additional opportunities for targeting this receptor safely.
As research continues in this area, the medical community eagerly awaits the outcomes of ongoing clinical trials involving lidocaine and its potential to transform the treatment landscape for head and neck cancers.
