RESEARCH UPDATE- Texas Children’s Hospital/ Baylor College of Medicine.

Researchers: Ling Tao, PhD and Eveline Bargieri, MD, PhD

Research project: Targeting Glutaminolysis to Overcome Neuroblastoma Resistance to mTOR Inhibition

Neuroblastoma (NB), similar to other solid tumors, grows in a harsh microenvironment with lack of oxygen and nutrients. However, tumors with high expression of a gene called MYCN (the primary driver of NB growth) survive, evade treatment, and eventually progress, resulting in less than 50% survival rate. How MYCN helps tumor survive and grow remains poorly understood.

Our research has shown that MYCN promotes the consumption of glutamine, a nutrient that is essential for NB cell survival and drug resistance. When we block a key enzyme in glutamine metabolism called glutaminase 1 (GLS1), using a clinically available drug (CB-839) has the potential to overcome the factors that drive NB growth.

We also know that another signaling pathway called mTORC1 promotes NB cell growth. Temsirolimus (TEM) is a drug that can inhibit mTORC1 signaling.

In this study, we are using a sophisticated tool known as “metabolomics” to assess how MYCN allows NB cells to grow. This data will subsequently be used to evaluate the anti-tumor activity of combinations of novel drugs in pre-clinical models of NB to see if we can restore the sensitivity of the tumor to the standard treatments that inhibit NB cell growth.

We have made substantial progress in completing the first Aim and over the next year, we will focus on evaluating these novel treatment approaches to assess if we can restore the sensitivity of NBs with high MYCN expression.

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Did You Know

Building awareness of childhood cancer is critical to funding and finding a cure. To help, please consider sharing on your Facebook.

Today, 46 children will be diagnosed with cancer.  Seven will lose their battle.

Did you know September is National Childhood Cancer Awareness Month!

Every day in America, approximately 46 children are diagnosed with cancer.

Childhood cancer does not discriminate, sparing no ethnic group, socio-economic class, or geographic region.

Rhabdomyosarcoma is the most common soft tissue sarcoma in children, accounting for about 3% of childhood cancers.

On average, 1 in every 4 elementary schools has a child with cancer.

About one-third of childhood cancers are leukemias.

Childhood cancer survival rates in the United States have increased from less than 20% in the 1960s to almost 80% today.

Cancer kills more children each year than Asthma, Cystic Fibrosis, Diabetes, and Pediatric AIDS combined.

Childhood cancer is not one disease entity, but rather a spectrum of different malignancies. Cancers found in children are biologically different from those seen in adults.

1 in 300 children will develop cancer before age 20.

Neuroblastoma is the most common extra cranial solid tumor cancer in children.

Today, up to 75% of the children with cancer can be cured, yet, some forms of childhood cancers have proven so resistant to treatment that, in spite of research, a cure is illusive.

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