Targeting Nerve Cells Might Offer New Way to Fight Mesothelioma, Other Cancers

Israeli scientists may have found a new way to fight mesothelioma and other cancers from the inside out by targeting nerve cells. 

Researchers at Technion – Israel Institute of Technology conducted the new study. It appears in the journal Science Advances. 

Nerve cells called neurons help promote tumor growth. The team reasoned that targeting these tumor nerve cells with a damaging drug might slow cancer progression. 

They tested the theory on triple-negative breast cancer tumors in mice. The tumors still grew but they grew much slower than the untreated tumors. The findings could have implications for other hard-to-treat cancers like malignant mesothelioma. 

New Options Needed for Malignant Mesothelioma

Malignant mesothelioma is one of the rarest and most treatment-resistant cancers. Many people who contract mesothelioma survive for less than a year, even with the best treatments. For this reason, scientists around the world are constantly looking for new ways to treat mesothelioma.

The idea of targeting nerve cells is different from any of the current mesothelioma therapies. Right now, most people start with chemotherapy with Alimta (pemetrexed) and cisplatin. If that does not work, patients might try a different chemotherapy drug like gemcitabine. 

Immunotherapy is another up-and-coming treatment option for mesothelioma. Immunotherapy drugs like Yervoy and Opdivo seem to be most effective for mesothelioma patients whose tumors express high levels of certain proteins. 

A downside of both of these approaches to mesothelioma is that they are systemic. The drugs go throughout the whole body. This increases the risk of serious side effects. 

Targeting nerve cells in the way the Israeli scientists did may cause fewer side effects. They used nanoparticles to deliver the drug directly to the neurons in tumors. This way, healthy cells are less likely to be affected. 

A Novel Way of Targeting Nerve Cells in Tumors

Scientists at Technion created lipid nanoparticles to act as a delivery system. They loaded these nanoparticles with a non-opioid analgesic called bupivacaine. Then they delivered it into breast cancer tumors in mice. 

The goal was to “suppress nerve-to-cancer cross talk” that helps tumors grow.

“Signaling between triple-negative breast cancer cells (4T1) and neurons involves secretion of cytokines stimulating neurite outgrowth,” writes lead researcher Maya Kaduri. “Reciprocally, neurons stimulated 4T1 proliferation, migration, and survival through secretion of neurotransmitters.”

Bupivacaine curbs neuron growth and signaling in cancer cells, making them less viable. 

The team found that the targeted cells readily absorbed the drug and cancer cell growth slowed way down. In fact, targeting nerve cells slowed tumor growth by more than half over untreated tumors. 

“We wanted to reduce the aggressiveness of tumors by killing the nerve cells that are inside the tumor tissue, and we succeeded in doing exactly this,” Dr. Kaduri told The Times of Israel. “This is very exciting and novel.”

The report concludes that targeting nerve cells “is important for treating cancer”.

Sources:

Kaduri, M, et al, “Targeting neurons in the tumor microenvironment with bupivacaine nanoparticles reduces breast cancer progression and metastases”, October 6, 2021, Science Advances, Volume 7, Issue 4, https://www.science.org/doi/10.1126/sciadv.abj5435

Jeffay, Nathan, “Israeli scientists halve growth of cancer tumors in mice, using ‘GPS particles’”, October 22, 2021, The Times of Israel, https://www.timesofisrael.com/israeli-scientists-halve-growth-of-cancer-tumors-in-mice-using-gps-particles/