LSU Health New Orleans research finds new Rx target for childhood cancer

New Orleans, LA – Research led by Michael Lan, PhD, Professor of Pediatrics and Genetics at LSU Health New Orleans School of Medicine, found that a compound named 5′-iodotubercidin (5′-IT) suppresses the growth of neuroblastoma cells and identified a potential new therapeutic approach for the disease. The paper, currently available online here, will be published in the April 12, 2019, issue of the Journal of Biological Chemistry.

Neuroblastoma is the most common non-brain solid tumor in children. It is a cancer of neuroendocrine cells – cells that have characteristics of both nerve cells and hormone-producing cells. Neuroblastomas start in immature nerve cells, called neuroblasts, of the sympathetic nervous system. They form when there are abnormal changes in the genes controlling the development of these young cells into specialized cells. While some neuroblastomas resolve on their own, others can be fatal. The objective of the research was to find a new drug for the treatment of aggressive neuroblastoma tumors.

Dr. Lan’s laboratory studies a DNA-binding protein, INSM1, made from the gene that regulates the development of immature or undifferentiated neuroendocrine cells. INSM1 is activated by another protein called N-Myc, and both are overproduced in neuroblastoma.

“Too much N-Myc occurs in roughly 30% of neuroblastoma tumors and strongly correlates with advanced-stage disease and poor outcome,” Lan notes. “INSM1 has emerged as a critical factor in neuroblastoma cell growth.”

The researchers were looking for a compound that would suppress excessive INSM1 and discovered that 5′-IT inhibits INSM1 protein expression and also affects cellular signaling molecules leading to neuroblastoma cell death.

“Taken together, we developed a unique INSM1 promoter-driven reporter assay to identify drugs that specifically inhibit INSM1 promoter activity,” concludes Lan. “The identification of new signaling pathways that control the proliferation of aggressive neuroblastoma suggests new options for combination therapy of neuroblastoma patients.”

According to the American Cancer Society, neuroblastoma accounts for about 6% of all cancers in children. There are about 800 new cases of neuroblastoma each year in the United States. The average age of children when they are diagnosed is about 1 to 2 years. In rare cases, neuroblastoma is detected by ultrasound even before birth. Nearly 90% of cases are diagnosed by age 5. In about two of three cases, the disease has already spread to the lymph nodes or to other parts of the body when it is diagnosed.

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The research team also included Chiachen Chen, PhD, Mary B. Breslin, PhD., Jessie J. Guidry, BS, in the Departments of Pediatrics, Genetics, Biochemistry and Molecular Biology at LSU Health New Orleans School of Medicine.

The research was supported by National Cancer Institute the Louisiana State University Research Enhancement Program, LSU Health New Orleans School of Medicine and Children’s Hospital, New Orleans.

LSU Health Sciences Center New Orleans educates Louisiana’s health care professionals. The state’s flagship health sciences university, LSU Health New Orleans includes a School of Medicine, the state’s only School of Dentistry, Louisiana’s only public School of Public Health, and Schools of Allied Health Professions, Nursing, and Graduate Studies. LSU Health New Orleans faculty take care of patients in public and private hospitals and clinics throughout the region. In the vanguard of biosciences research in a number of areas in a worldwide arena, the LSU Health New Orleans research enterprise generates jobs and enormous economic impact. LSU Health New Orleans faculty have made lifesaving discoveries and continue to work to prevent, advance treatment, or cure disease. To learn more, visit http://www.lsuhsc.edu, http://www.twitter.com/LSUHSCHealth or http://www.facebook.com/LSUHSC.

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Related Journal Article

http://lsuh.sc/nr?a=1601
http://dx.doi.org/10.1074/jbc.RA118.006761

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