DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

National Childhood Cancer Awareness Month: Advancing Research in More Than 13 Types of Childhood Cancers, Including Neuroblastoma

Posted September 12, 2023

Dr. Tao Liu, University of South Wales

Dr. Tao Liu Dr. Tao Liu (Photo Provided)

Childhood cancer, also known as pediatric cancer, are a group of rare cancers that affect children and teens from birth to age 19. More than 15,000 children and teens are estimated to be diagnosed with cancer each year.1 Cancer is the leading cause of death by disease for children in the United States with more than 1,600 children and teens losing their lives each year.2 September has been officially recognized as National Childhood Cancer Awareness month, throughout the world, to bring awareness to childhood cancers, the Families affected by these cancers, and those working to prevent, treat, and improve the lives of childhood cancer patients. The Rare Cancers Research Program (RCRP) funded 26 projects towards impactful research related to more than 13 childhood cancers since its inception in 2020.

Dr. Tao Liu Figure 1. Methyltransferase induces neuroblastoma progression in mice. Neuroblastoma cells were injected into nude mice. When tumors reached 0.05 cm3 in volume, the mice were divided into two groups and fed with food to knockdown methyltransferase expression. Tumor growth was monitored every other day, and the mice were sacrificed when the tumor reached 1 cm3. Survival curve analysis showed the probability of mouse overall survival. Two-sided log-rank test was used to generate the p -value. (Diagram Provided)

In FY20, Dr. Tao Liu, from the University of New South Wales, received a RCRP Idea Development Award to investigate a novel therapeutic approach in neuroblastoma, which is the most common cancer in infants with the average age of diagnosis before 2 years old. In neuroblastoma, cancer develops in early nerve cells, most usually in the abdomen, in the adrenal gland, or sympathetic nerves.3 Dr. Liu and his team sought to understand the role of an enzyme, ribonucleic acid (RNA) methyltransferase, in neuroblastoma survival and progression to determine if inhibition of this methyltransferase can treat neuroblastoma. Methyltransferases are enzymes which add methyl groups to a substrate, in this case RNA molecules. The addition of the methyl group leads to changes in how the RNA is processed into proteins.

Dr. Liu and his team depleted methyltransferase in a neuroblastoma cell by knocking down the methyltransferase gene, and identified reduced neuroblastoma cell growth and proliferation in vitro. Depleted neuroblastoma cells were injected into mice and tumor growth were monitored. Tumors formed at a significantly slower rate by the depleted neuroblastoma cells compared to the neuroblastoma cells with normal methyltransferase expression. Mice injected with methyltransferase-deficient neuroblastoma cells also had increased probability of survival, compared to mice injected with normal neuroblastoma cells (Figure 1).

The tumor study in mice demonstrates how methyltransferase plays an important role in neuroblastoma development. Subsequently, the team will use human neuroblastoma tissues to determine if methyltransferase expression can serve as a biomarker for patient prognosis. At the same time the research team will also complete drug screening to identify drugs that may inhibit methyltransferase and could serve as a novel therapeutic in neuroblastoma.


References:

1American Society of Clinical Oncology, Cancer.Net. Childhood Cancer: Statistics. https://www.cancer.net/cancer-types/childhood-cancer/statistics

2National Cancer Institute. Cancer in Children and Adolescents. https://www.cancer.gov/types/childhood-cancers/child-adolescent-cancers-fact-sheet

3American Cancer Society. What Is Neuroblastoma? https://www.cancer.org/cancer/types/neuroblastoma/about/what-is-neuroblastoma.html


Links:
Public and Technical Abstracts: The RNA Methyltransferase METTL5 as a Novel Target for Cancer Therapy








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Last updated Tuesday, September 12, 2023