Israeli doctors treat hypoglycemia in lung cancer with breast cancer drug

Working with Technion researchers, endocrinologists and oncologists prove effectiveness of alpelisib in reversing severe hypoglycemia caused by large tumors

Renee Ghert-Zand is the health reporter and a feature writer for The Times of Israel.

From left: Dr. Matan Fisher, Prof. Gil Leibowitz, and Prof. Avivit Cohen from Hadassah Medical Center (Courtesy of Hadassah Medical Center)
From left: Dr. Matan Fisher, Prof. Gil Leibowitz, and Prof. Avivit Cohen from Hadassah Medical Center (Courtesy of Hadassah Medical Center)

A breast cancer drug can be used to treat severe hypoglycemia in patients with lung cancer, a team of physicians at Jerusalem’s Hadassah Medical Center together with researchers at the Technion in Haifa has found.

Until now, one of the only ways to treat a cancer patient’s precipitous drop in blood sugar levels was for them to undergo continuous glucose infusions. Steroids and other medications have rarely worked in treating the rare condition and they can include unpleasant side effects.

The Israeli researchers’ findings, which focus on a molecular pathway shared by breast cancer and large cancer tumors that secrete glucose into muscle, were recently published in the prestigious New England Journal of Medicine.

The study cites the case of a 57-year-old with lung cancer who arrived at Hadassah Medical Center’s emergency room in 2021 with severe hypoglycemia.

Unlike in diabetics, his low blood sugar was not caused by too much insulin but by the secretion of a specific protein produced by his tumor, which radically increases glucose uptake in the body’s muscle tissue.

“This is a rare complication of cancer, and it usually happens in patients with very large tumors, and not only in the lungs. Usually, it’s a type of cancer that we call mesenchymal tumors,” said Prof. Gil Leibowitz.

Hadassah Medical Center in Ein Kerem, Jerusalem on August 17, 2021. (Yonatan Sindel/Flash90)

Leibowitz, head of Hadassah’s diabetes center, worked quickly with a team of colleagues — endocrinologists and oncologists — to find a solution for the patient, who was at risk of suffering confusion, blurred vision, change in behavior, seizures and even death.

Caused by the tumor’s secretion of the pro-IGF2 protein, this type of hypoglycemia has very severe implications for an individual’s quality of life and is difficult to address.

“With diabetes, if there is low blood sugar caused by excess insulin, you eat carbohydrates and it’s gone. With this, it doesn’t go away,” he said.

The team of physicians zeroed in on the fact that the signaling pathway by which pro-IGF2 activates glucose to the muscle is the same one involved in cell growth in cancer progression. The physicians’ goal was to inhibit this pathway, and they realized that alpelisib does this when used to treat breast cancer.

“The mechanism was never proven, but we knew we had nothing to lose,” said Leibowitz. “The patient’s condition was deteriorating, and we had to think out of the box and act immediately.”

The patient’s sugar levels reportedly stabilized in a few hours, and as the doctors experimented to find the correct dosage, the patient did not experience any further hypoglycemia.

Illustrative: A woman getting her blood sugar level checked in Indonesia, November 13, 2019. (ADEK BERRY / AFP)

Treatment with the drug costs tens of thousands of dollars, which was not affordable for the patient. At first, the drug company, Novartis, responded negatively to an off-label use request due to a lack of literature on alpelisib’s employment for this purpose.

“After we were able to get a supply of the drug from Friends of Health (an organization that provides free medications), conducted tests, and provided data on our success, the drug company changed its mind and provided the patient the drug, which is taken orally,” Leibowitz said.

The Hadassah group then turned to colleagues at the Technion’s Tissue and Stem Cell Engineering Laboratory for help in demonstrating the mechanism behind the drug’s efficacy for hypoglycemia.

“They have a system where they grow human muscle cells in three-dimensional scaffolds. And we were able to show that the pro-IGF2, which indeed increased, activates the pathway and increases glucose uptake to muscle and that the medication can inhibit that uptake,” Leibowitz said.

The patient continued to take the medication but unfortunately died several months later because of his tumor’s progression. However, the positive results of his treatment with the breast cancer drug for his hypoglycemia can help other cancer patients with the same complication.

Leibowitz suggested that alpelisib may be especially applicable for patients with cancer that starts in the pancreas and can spread to the liver.

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