2023-08-17 14:09:28
A team of doctors from Hadassah Hospital in Jerusalem and researchers from the Technion in Haifa have discovered that a breast cancer drug can be used to treat severe hypoglycemia in patients with lung cancer.
Until now, one of the only ways to treat a sudden drop in blood sugar levels in a cancer patient was to give them continuous infusions of glucose. Steroids and other medications are rarely effective in treating this rare condition and can have unpleasant side effects.
The Israeli researchers’ findings, which relate to a molecular pathway common to breast cancer and large cancerous tumors that secrete glucose into muscles, were recently published in the prestigious New England Journal of Medicine.
The study cites the case of a 57-year-old man with lung cancer who presented to the emergency room at Hadassah Hospital in 2021 with severe hypoglycemia.
Unlike diabetics, his hypoglycemia was not due to an excess of insulin, but to the secretion of a specific protein produced by his tumor, which radically increases the uptake of glucose in the muscle tissues of the body.
“This is a rare complication of cancer, which usually occurs in patients with very large tumours, and not just in the lungs. It’s usually a type of cancer that we call a mesenchymal tumor,” said Professor Gil Leibowitz.
Hadassah Ein Kerem Hospital in Jerusalem on August 17, 2021. (Yonatan Sindel/Flash90)
Leibowitz, director of the Hadassah Diabetes Center, quickly worked with a team of colleagues – endocrinologists and oncologists – to find a solution for the patient, who was at risk of suffering from confusion, blurred vision, behavior change , epileptic seizures and even death.
Caused by the secretion of the pro-IGF2 protein by the tumour, this type of hypoglycaemia has very serious consequences on the individual’s quality of life and is difficult to treat.
“With diabetes, if you have hypoglycemia caused by too much insulin, you eat carbohydrates and the hypoglycemia goes away. In the case of this disease, it does not go away,” he said.
The team of doctors focused on the fact that the signaling pathway by which pro-IGF2 activates glucose in muscle is the same one involved in cell growth in cancer progression. The doctors’ goal was to inhibit this pathway, and they found that alpelisib – achieved this when used in the treatment of breast cancer.
“The mechanism has never been proven, but we knew we had nothing to lose,” says Dr. Leibowitz. “The patient’s condition was deteriorating and we had to think outside the box and act immediately. »
The patient’s blood sugar levels stabilized within hours, and while doctors tried to find the right dosage, the patient did not experience further hypoglycemic attacks.
Illustrative: A woman having her blood sugar checked in Indonesia on November 13, 2019. (Adek Berry/AFP)
This treatment costs tens of thousands of dollars, which was beyond the reach of the patient. Initially, the pharmaceutical company, Novartis, responded negatively to a request for off-label use due to a lack of documentation on the use of alpelisib for this purpose.
“After obtaining the drug from Friends of Health (an organization that provides free medication), and conducted tests and provided data on our success, the pharmaceutical company changed its mind and provided the patient with the medication, which is taken orally,” Leibowitz said.
Hadassah’s group then turned to colleagues at the Technion’s Tissue and Stem Cell Engineering Laboratory to help demonstrate the mechanism behind the drug’s effectiveness against hypoglycemia. .
“They have a system for growing human muscle cells in three-dimensional supports. We were able to show that the actually increased pro-IGF2 activates the pathway and increases muscle glucose uptake and that the drug can inhibit this uptake,” Leibowitz said.
The patient continued to take the drug, but unfortunately died a few months later due to tumor progression. However, the positive results of her treatment with the breast cancer drug for her hypoglycemia may help other cancer patients with the same complication.
Leibowitz suggested that alpelisib could be particularly useful for patients with cancer that starts in the pancreas and can spread to the liver.
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