Madhavi Bhatia, National Institute of Pharmaceutical Education and Research Guwahati
Neuroblastoma is a form of solid tumour found in children. It accounts for about 15% of total cancer-related deaths in children. These tumours develop from a certain type of nerve cells and are found in the abdomen. The current treatment for patients with severe neuroblastoma is chemotherapy followed by surgical resection or radiotherapy. Children who are above the age of one and diagnosed with neuroblastoma often fail to respond even to the most aggressive combination of therapy or relapse later. Thus there is a need for alternative treatments.
MYCN gene as an oncogenic driver of neuroblastoma
In research published in Advanced Functional Materials, it was observed that there was gene amplification or mutation of the MYCN gene in about 20% of neuroblastoma cases. The MYCN gene is usually expressed during the fetal development stage of neurogenic tissue. It encodes for N-Myc, a member of the Myc family of transcription factors, controlling the expression of the genes involved in cell proliferation, growth, metabolism, protein synthesis, and apoptosis. The continuous expression of the MYCN gene in the neuroblastoma cells, which leads to uncontrolled cell growth and thus prevents cancer cells from dying.
Along with the MYCN gene, there are 2 components of the molecular clock that are repressed during neuroblastoma –BMAL1, which oscillates to drive the clock cycle, and RORa, which activates BMAL1. The repression leads to a poor clinical outcome. It was found that the MYCN amplification leads to inhibition of BMAL1 expression and oscillation, which leads to metabolic reprogramming and oncogenesis.
MYCN-targeted siRNA treatment
Various researches are going to develop ways to silence the MYCN gene and to develop a target-specific treatment for neuroblastoma. One of which includes short-interfering RNA (siRNA)-mediated MYCN silencing, cell differentiation, or apoptosis. This si-RNA-mediated treatment can be achieved by systemic administration of the siRNA in the form of a suitable nanoparticle formulation. Neuroblastoma tumours are highly vascularized and have leaky endothelium which allows the nanoparticles to enter into the tumour from the blood vessels or by endothelial transcytosis. Most of the nanoparticles delivered via injection into the tumour successfully silence the MYCN gene causing cancer. The treatment resulted in the growth of tumour cells at a slower pace and increased the survival time.
Conclusion
Current therapies such as chemotherapy, radio, and surgery are effective in removing the primary tumour but in many cases, there are chances of relapsing of tumour at the other sites of the body, which is quite harder to treat. Thus, this MYCN –targeted siRNA treatment has emerged as a new potential therapy that might augment conventional therapies and help in reducing the deaths of children due to neuroblastoma.
Also read: Treatment of Lymphoma in Dogs- Fully granted by FDA for the first time
Reference
1. London, U. C. (n.d.). Tiny bubbles used to treat common childhood cancer. Retrieved July 29, 2021, from https://medicalxpress.com/news/2021-07-tiny-common-childhood-cancer.html
2. Tagalakis, A. D., Jayarajan, V., Maeshima, R., Ho, K. H., Syed, F., Wu, L., Aldossary, A. M., Munye, M. M., Mistry, T., Ogunbiyi, O. K., Sala, A., Standing, J. F., Moghimi, S. M., Stoker, A. W., & Hart, S. L. (2021). Integrin‐targeted, short interfering rna nanocomplexes for neuroblastoma tumor‐specific delivery achieve mycn silencing with improved survival. Advanced Functional Materials, 2104843. https://doi.org/10.1002/adfm.2021048433.
3. University, B. (2021, July 28). Turning the molecular clock back on halts neuroblastoma tumor growth. ScienceBlog.Com. https://scienceblog.com/524417/turning-the-molecular-clock-back-on-halts-neuroblastoma-tumor-growth/
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About the author
Madhavi Bhatia is currently pursuing a Master of Science in Pharmaceutical Biotechnology from NIPER, Guwahati. Her area of interest lies in understanding the role of gene mutation in the development of various diseases and developing a treatment for such diseases.
Publications
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