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Lidocaine May Activate Bitter Taste Receptors To Kill Cancer Cells

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The common numbing agent lidocaine can activate bitter taste receptors leading to cancer cell death, according to a new study from the University of Pennsylvania. The research, published in Cell Reports, could lead to clinical trials of lidocaine alongside standard treatments for head and neck cancers.

Lidocaine’s potential anti-cancer properties

It was already known that the local anesthetic drug lidocaine may have anti-cancer properties, but it was unclear exactly how and why.

Lidocaine is commonly injected into the skin or other tissues to prevent pain by blocking nerve signals and has the potential to be injected into or around accessible oral tumors.

A previous study showed that bitter taste receptors are found in many oral and throat cancer cells, where they trigger cell death via a process called apoptosis. Patients with head and neck cancers that express higher levels of these bitter taste receptors are associated with better survival. Additionally, a recent clinical trial found that administering lidocaine before surgery increased survival rates for breast cancer patients.

The researchers in the current study, led by senior authors Dr. Robert Lee and Dr. Ryan Carey, investigated the effect of lidocaine on lab-grown head and neck squamous cell carcinoma (HNSCC) cells.

Activation of bitter taste receptors

They found that lidocaine activates a bitter taste receptor called T2R14, which is elevated in certain cancer types. T2R14 activation causes an overload of calcium ions in the mitochondria, producing reactive oxygen species that damage cells and leading to proteasome inhibition. Together, this leads cancer cells to die via apoptosis.

“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,” said Lee. “T2R14 is found in cells throughout the body. What’s incredibly exciting is that a lot of existing drugs activate it, so there could be additional opportunities to think about repurposing other drugs that could safely target this receptor.”

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Furthermore, the team found that T2R14 is particularly elevated in HNSCCs associated with infection with the human papillomavirus (HPV), one of the major forms of HNSCC.

“Speaking as a head and neck surgeon, we use lidocaine all the time,” said Carey. “We know lidocaine is safe, we’re comfortable using it, and it’s readily available, which means it could be incorporated into other aspects of head and neck cancer care fairly seamlessly.”

However, while T2R14 receptors in the mouth allow us to perceive bitter tastes, researchers are unsure of their function in other locations throughout the body.

Opening up avenues for clinical trials

Carey now has plans to carry out a clinical trial to test lidocaine alongside standard treatments for HPV-associated HNSCCs.

“While we’re not suggesting the lidocaine could cure cancer, we’re galvanized by the possibility that it could get an edge on head and neck cancer treatment and move the dial forward, in terms of improving treatment options for patients with this challenging form of cancer,” explained Carey.

Reference: Miller ZA, Mueller A, Kim T, et al. Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14. Cell Reports. 2023. doi: 10.1016/j.celrep.2023.113437

This article is a rework of a press release issued by Penn Medicine. Material has been edited for length and content.