A new study identifies an Achilles’ heel in neuroblastoma. 15% of children who die from Childhood Cancer are victims of neuroblastoma,

Researchers Discover a Key Weak Spot in a Deadly Childhood Cancer

A childhood cancer that arises from neural cells on the adrenal glands. Nearly 50% of kids with high-risk neuroblastoma have additional copies of the MYCN (MYCN amplified) gene, which is the main driver of neuroblastoma and its resistance to treatment. “Treating neuroblastoma by directly targeting MYCN has been challenging,” said Dr. Eveline Barbieri, corresponding author of a recent study published in Nature Communications and assistant professor of pediatrics – hematology and oncology at Baylor College of Medicine and Texas Children’s Hospital. “In this study, we investigated new strategies to improve the survival of children with MYCN amplified neuroblastoma by looking into metabolic vulnerabilities that we could exploit to overturn these tumors’ resistance to therapy.” Barbieri and her colleagues compared the metabolic profiles of MYCN-amplified neuroblastomas to the profiles of non-MYCN-amplified neuroblastomas using an unbiased, metabolomics analysis. Their novel methodology revealed important differences between the two tumor groups in the way tumor cells used certain nutrients to fuel tumor development.

“We found that MYCN amplification rewires a tumor’s lipid metabolism in a way that promotes the use and biosynthesis of fatty acids, a type of lipid cells can use as a source of energy,” Barbieri said. “Cells with extra copies of MYCN depend highly on fatty acids for their survival. Childhood Cancer, We confirmed this both in MYCN-amplified cell lines and in MYCN- amplified patient tumor samples.” Barbieri and her colleagues proposed that MYCN reroutes lipid metabolism to make fatty acids easily accessible to cancer cells, encouraging the growth of tumor cells. “When we investigated what prompted MYCN-amplified neuroblastomas to rely on fatty acids to grow, we discovered that MYCN directly upregulates or enhances the production of fatty acid transport protein 2 (FATP2), a molecule that mediates cellular uptake of fatty acids,” Barbieri said. “We then asked, what would happen if we interfered with FATP2 function in MYCN-amplified neuroblastomas?” When the researchers neutralized FATP2 activity, either by knocking down the gene or by blocking FATP2 action with a small-molecule inhibitor, they reduced the growth of MYCN-amplified tumors. “We observed that when we blocked the import of fatty acids into the cancer cells, there was a reduction in tumor cell growth,” Barbieri said. “The interesting part is that inhibiting or blocking FATP2 had no effect on normal cells or tumors without MYCN-amplification. This seems to be a selective metabolic vulnerability of MYCN-amplified tumors. They uniquely use this transporter to feed on fatty acids to grow.”

Source: This news is originally published by scitechdaily

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