Cutting-edge research to find a cure for patients with metastatic neuroendocrine tumors

Dr. Simona Glasberg, M.D. Head, Neuroendocrine Tumor Unit, Endocrinology & Metabolism Department,

Neuroendocrine tumors (NETs) are abnormal growths that begin in neuroendocrine cells, which are distributed throughout the body. These cells secrete hormones in response to neural stimulation. Neuroendocrine tumors can develop differently in many places in the body. Many NETs first appear in the lungs or the gastrointestinal tract, including the stomach, pancreas, appendix, intestines, colon and rectum. NETs may also appear in the thymus, thyroid gland, adrenal gland, ovaries, kidneys and pituitary gland. Metastatic NETs, wherein tumors have spread into nearby lymph nodes or other organs, have unfavorable prognosis and are relatively frequent, occurring in up to 60% of the patients. The liver is the most common site of metastases (82% of patients with metastases), and the small intestine is one of the most common sources of NET metastases. The incidence of NETs is approximately 6.9/100,000. Although an increased incidence of neuroendocrine tumors has been reported worldwide, the reasons underlying this rise have not been fully identified, and NETs remain a poorly understood disease. Unfortunately, many patients with metastatic NETs fail to respond to currently available therapies, due to the development of treatment resistance. While most of the therapies slow down tumor progression, the effect is usually transient, without inducing significant and persistent tumor regression.

Dr. Simona Glasberg from the Neuroendocrine Tumor Unit at Hadassah is undertaking a very important investigation using inhibitors (termed mTOR inhibitors) which affect a pathway called PI3kinase/Akt/mTOR; this pathway is involved in the acceleration of tumor growth. It is well known that mTOR plays a pivotal role in governing cell growth and proliferation, hence making it a therapeutic target for disease conditions caused by deregulated cell proliferation, such as cancer. In fact, in the past decade, numerous mTOR inhibitors have been developed and many are currently in clinical trials for cancer treatment. However, mTOR inhibitors induce autophagy, a cell survival mechanism promoting cancer cell survival. Therefore, Dr. Glasberg aims to examine the effect of mTOR inhibitors in combination with autophagy inhibitors in three NET mouse models. Preliminary results of this investigation are promising, and Dr. Glasberg fervently believes that this drug combination might cause tumor regression.

Due to the lack of therapeutic strategies to treat metastatic NETs, the investigation carried out by Dr. Simona Glasberg and her team is indeed significant and worthy of support for the development of effective therapeutic combinations to overcome drug resistance in these patients. This research is a mandatory step for the development of possible clinical trials in NET patients with unmanageable disease. Of note, Apple Co-founder Steve Jobs died as a result of metastatic NET, which could not be stopped despite different treatments available at that time.

Dr. Simona Glasberg, a NET specialist, is the Director of the Neuroendocrine Tumor Unit, Dept. of Endocrinology at Hadassah. She has authored and co-authored multiple peer-reviewed scientific papers and has presented her research at many national and international conferences. Dr. Simona Glasberg is actively associated with different societies and academies and has received several sought-after awards. She believes that the ultimate physician will not only treat a patient who has the disease, but will also look beyond the individual patient to understand the mechanism of the disease, and eventually find a cure. In fact, this is what she is aiming for in patients with NETs.

The Hadassah’s Neuroendocrine Tumor Unit is a global leader in NET treatment and research; it is also one of the few medical centers in the world that uses Peptide Receptor Radionuclide Therapy (PRRT), a novel nuclear medicine therapy for metastasized neuroendocrine tumors. To date, you cannot get this treatment in many centers in the US, and patients come from the US come to be treated for this deadly disease in Hadassah.