Common anesthetic ‘Lidocaine’ can kill cancer cells, study finds

Lidocaine, commonly used to numb during outpatient medical procedures, triggers specific taste receptors in a way that kills cancer cells, according to scientists from the Perelman School of Medicine.

The study, outlined in Cell Reports, sets the stage for testing lidocaine alongside standard therapy for head and neck cancer patients. While lidocaine has been proposed as beneficial for cancer patients, the mechanism behind its effects was unclear.

Robert Lee and Ryan Carey, both assistant professors of Otorhinolaryngology—Head & Neck Surgery, along with Zoey Miller, a graduate student in pharmacology at Penn, found that lidocaine activates a taste receptor called T2R14, which is more prevalent in various cancer cells.

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life.

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Activation of this receptor initiates a process known as apoptosis, leading to the death of cancer cells. Lidocaine activates T2R14 through two mechanisms: mitochondrial calcium ion overload, which generates reactive oxygen species damaging to biomolecules, and proteasome inhibition, culminating in cell death.

Previous work by the team revealed bitter taste receptors in many oral and throat cancer cells, where they prompt apoptosis.

Additionally, heightened expression of these receptors correlates with better survival rates in head and neck cancer patients. A randomized clinical trial, published in the Journal of Clinical Oncology in April 2023, demonstrated increased survival in breast cancer patients who received lidocaine before surgery.

“We've been investigating this for years but were surprised to find that lidocaine targets the most highly expressed receptor across cancers,” Lee remarks. “T2R14 is present in cells throughout the body. What’s truly exciting is that many existing drugs activate it, suggesting opportunities to repurpose other drugs that could safely target this receptor.”

Head and neck cancer refers to a group of cancers that develop in the tissues of the head and neck region, including the mouth, throat, nose, sinuses, voice box (larynx), thyroid gland, salivary glands, and lymph nodes in the neck. The types of head and neck cancer include:

Oral Cavity Cancer: This type of cancer develops in the mouth, including the lips, gums, tongue, inside lining of the cheeks, roof of the mouth (palate), and floor of the mouth.

Pharyngeal Cancer: Pharyngeal cancer occurs in the pharynx, which is the hollow tube inside the neck that starts behind the nose and leads to the esophagus (the tube that carries food to the stomach). It includes three parts:

Laryngeal Cancer: Laryngeal cancer develops in the larynx, commonly known as the voice box. It includes three main parts:

Nasal Cavity and Paranasal Sinus Cancer: These cancers develop in the nasal cavity (the space behind the nose) and the paranasal sinuses (small hollow spaces around the nose).

Salivary Gland Cancer: Salivary gland cancer forms in one of the major or minor salivary glands, which produce saliva.

Thyroid Cancer: Thyroid cancer starts in the thyroid gland, a butterfly-shaped gland located in the front of the neck.

Sinus Cancer: Sinus cancer develops in the sinus cavities, which are air-filled spaces in the skull.

Metastatic Head and Neck Cancer: This type of cancer occurs when cancer cells spread from another part of the body to the head or neck region.

Each type of head and neck cancer may have different risk factors, symptoms, and treatment options. Early detection and treatment are crucial for improving outcomes in head and neck cancer patients.

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