Discovery of a compound that inhibits the growth of neuroblastoma cells

Researchers at Louisiana State University Health New Orleans Medical School have discovered that a compound called 5'-iodotubercidin(5'-IT)  inhibits the growth of neuroblastoma cells and determines the possibility of the compound. Provide new treatments for the disease. The study was published in the Journal of Biochemistry. 

Neuroblastoma is the most common extracranial solid tumor affecting children. It is developed from the early nerve cells of the sympathetic nervous system (also called neuroblasts), so when the genes that control the development of these immature cells into specialized cells are mutated, neuroblastomas are formed. Neuroblastoma is a neural network that transmits information about the entire brain.

Neuroblastoma occurring in the brain is most common in the frontal and parietal lobe, the most common in the ridge of the sympathetic nervous system is the adrenal gland, but it can also be seen in the neck, chest, abdomen, and pelvic nerve tissue.

According to the American Cancer Society, neuroblastoma accounts for approximately 6% of all childhood cancers. There are approximately 800 new cases of neuroblastoma in the United States each year. Most children are diagnosed at the age of 5, and very few have detected neuroblastoma by ultrasound during the embryonic period. And about two-thirds of the cancer cells in patients already diagnosed have often metastasized.

Neuroblastoma is one of the lowest survival rates of all pediatric cancers, accounting for 15% of all pediatric cancer deaths. The initial symptoms are usually blurred and may include fatigue and loss of appetite, which is why it is difficult to diagnose. Although some neuroblastomas will go away on their own, unfortunately, other neuroblastomas can be fatal. The aim of the study was to find a new drug for the treatment of invasive neuroblastoma.

The researchers discovered a protein called INSM1, a sequence-specific DNA-binding transcriptional regulator that plays a key role in neurogenesis and neuroendocrine cell differentiation during embryonic and fetal development. And INSM1 is activated by another protein called N-Myc, both of which are found overproduced in neuroblastoma.

Excessive N-Myc occurs in approximately 30 percent of neuroblastoma tumors, which is closely associated with advanced disease and poor prognosis. INSM1 has become a key factor in the growth of neuroblastoma cells.

Therefore, the researchers began looking for compounds that inhibited excessive INSM1 and developed a unique INSM1 promoter-driven reporter assay to identify drugs that specifically inhibit the activity of the INSM1 promoter. Eventually, they found that 5'-IT inhibits the expression of INSM1 protein and also affects cellular signaling molecules that cause neuroblastoma cell death.

These findings identify new signaling pathways that control the proliferation of invasive neuroblastomas and offer new options for combination therapy in patients with neuroblastoma.