Chicago [US], The growth of nerve cells outside the brain is where neuroblastoma, a common childhood disease, begins. More than 40 percent of patients with high-risk neuroblastoma currently do not survive, despite the fact that a patient's chances of survival have increased with more aggressive treatment, according to a recent study in New Treatment Strategy for Neuroblastoma. This may involve focusing on RN changes associated with the condition. From the University of Chicago. In a new study published in Cell Reports, researchers have shown that the proliferation of neuroblastoma cells was inhibited by a pharmacological molecule that aims to block proteins that modify RN transcripts. The drug appears to be a promising therapeutic approach, it even inhibited the growth of neuroblastoma tumors in mice models “High-risk neuroblastomas are very difficult to treat with current approaches and survivors are at high risk for treatment-related toxicities.” There are risks, including serious chronic health conditions and second cancer," said Susan Cohn, MD, professor of pediatrics and senior author of the new study. "We are testing an entirely different therapeutic strategy using drugs. are those that alter gene expression by inhibiting RNA modifying proteins.If future studies validate your findings, this strategy could change our approach to treating neuroblastoma patients. Advances in genetic sequencing, data analysis, and chemical biology have identified countless genetic correlates of cancer, yet DNA does not tell the whole story. Sometimes, molecules are added to DNA bases and RNA transcripts that affect the way genes are expressed or how they are translated into proteins. These modifications in DNA and RNA act as molecular molecules. switches, which determine whether a gene is turned on or off, thus influencing cellular processes, tissue development, and disease progression Cohn and his team led the work of Chuan He, PhD, the John T. Wilson Distinguished Service Professor of Chemistry and In partnership with Professor of Biochemistry and Molecules.Biology at UChicago, she is a pioneer in the field of RNA and DNA modification research, known as epitranscriptomics and epigenetics, respectively, to study these effects in neuroblastoma. His laboratory has discovered new regulatory pathways through RNA methylation. One of the most common messenger RNA modifications is N6-methyladenosine (M6A) that is added to the RNA transcript by "writer" proteins, including a complex formed between methyltransferase-like 3 (METTL3). and methyltransferase-like 1 (METTL14). High levels of METTL3 and METTL14 are known to drive the growth of many adult cancers, so Cohn and he wanted to look at its effects in neuroblastoma.The team was led by Monica M. Pomaville, MD, a former pediatrician who trained with Cohn and. He and now a fellow at Children's Hospital O Philadelphia, showed that high levels of METTL3 expression in neuroblastoma tumors were associated with significantly lower survival rates in patients. Thi suggests that METTL3 may induce tumor growth. To investigate how METTL3 affects neuroblastoma, the team created a genetically modified version of neuroblastoma cells in which METTL3 expression was reduced, or reduced. They also tested an inhibitor called STM2457 that blocks the function of METTL3, synthesized by their team based on a published molecular structure.Both approaches reduced neuroblastoma cell growth. METTL3 inhibition increased the expression of genes that regulate the differentiation of neurons or development into mature cells. They also observed that it increased the extension of neurites, which eventually develop into axons and dendrites, a hallmark of neuroblastoma differentiation. The team also tested the STM2457 inhibitor in a mouse model with neuroblastoma and found that it also reduced tumor growth. Recently, inhibitors of METTL3 have been shown to enhance the anti-tumor effects of immunotherapy in adult cancer by promoting tumor infiltration of immune cells.When tumors infiltrate immune cells, they become inflamed, or "hot." Neuroblastoma is a non-T cell inflammatory, or "cold" tumor that is resistant to immunotherapy such as checkpoint blockade drugs.