Williams Cancer Institute



Squamous cell carcinomas of the head and neck (HNSCC) pose a significant global health challenge, with approximately 900,000 new cases annually and a 50% mortality rate within five years. The lack of early detection and high metastasis rates contribute to this high mortality, emphasizing the urgent need for effective therapies that enhance the quality of life (QoL) for patients.

Current treatments, including surgery, radiation, chemotherapy, and immunotherapy, often result in side effects affecting long-term survival. Given the predominant localization of HNSCC in taste-perceptive areas like the oral cavity and oropharynx, exploring the connection between taste perception and cancer biology becomes a relevant focus.

Bitter taste receptors (T2Rs), beyond their role in taste perception, are involved in innate immunity and other biological processes. T2R14 emerges as a key component, suggesting potential therapeutic applications.

A team of researchers from the Perelman School of Medicine at the University of Pennsylvania, led by Ryan Carey, MD, and Robert Lee, PhD, discovered that lidocaine, commonly used as an anesthetic for outpatient medical procedures, activates specific bitter taste receptors through two distinct mechanisms, resulting in cancer cell death.

In this study, lidocaine was found to mobilize intracellular calcium by activating T2R14 in HNSCC cells. T2R14 activation with lidocaine depolarizes mitochondria, inhibits proliferation, and induces apoptosis. Simultaneously, calcium influx into mitochondria and reactive oxygen species (ROS) production cause T2R14-dependent accumulation of polyubiquitinated proteins, suggesting that proteasome inhibition contributes to T2R14-induced apoptosis.

Lidocaine may have therapeutic potential in HNSCC, either as a topical gel or intratumoral injection. Additionally, it is noted that human papillomavirus-associated (HPV+) HNSCCs are associated with increased TAS2R14 expression.

These findings, published in Cell Reports, pave the way for a clinical trial to test the addition of lidocaine to standard therapy for head and neck cancer patients. While lidocaine has been suggested to have beneficial effects in cancer patients, the mechanisms were previously unknown. Lidocaine treatment could benefit these patients, justifying future clinical studies.

Reference 1: Zoey A. Miller, Arielle Mueller, TaeBeom Kim, Jennifer F. Jolivert, Ray Z. Ma, Sahil Muthuswami, April Park, Derek B. McMahon, Kevin T. Nead, Ryan M. Carey, Robert J. Lee, 26 December 2023, Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14, https://www.sciencedirect.com/science/article/pii/S2211124723014493
Reference 2: Penn Medicine, 22 November 2023, Lidocaine May Be Able to Kill Certain Cancer Cells by Activating Bitter Taste Receptors, https://www.pennmedicine.org/news/news-releases/2023/november/lidocaine-kills-cancer-cells-by-activating-bitter-taste-receptor

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