Dr. Anthony Graves, Young Investigator: Neuroblastoma

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Project: Therapeutically Targeting OPA1 in N-Myc Amplified Neuroblastoma

Sole Benefactor: Hope Street Kids

Neuroblastoma is a cancer of the sympathetic nervous system occurring primarily in young children. While low-risk cases have a high survival rate, children with later-stage neuroblastoma have much poorer outcomes. Neuroblastoma still accounts for more than 10% of all deaths in children with cancer.

Progress in treating this cancer has been challenging because researchers do not fully understand the mutations, or abnormalities, that occur in the genes that are responsible for neuroblastoma. The current treatments are highly toxic, yet often fail to treat the disease effectively. Anthony Graves, MD, PhD at the University of Pittsburgh, has recently been awarded a CureSearch Young Investigator grant for his research on a high-risk sub-type of neuroblastoma. Dr. Graves is studying new molecular targets in N-Myc amplified neuroblastoma, a sub-type of the disease known to have poor outcomes.

Anthony Graves
  • Anthony Graves, MD, PhD
  • University of Pittsburgh
  • Children’s Hospital of Pittsburgh

Dr. Graves studies the biology of a particular gene known to be involved in this high-risk sub-type. This gene, the Myc gene, is a promising target for anti-cancer drugs. Myc is a regulator involved in how cells replicate. Myc is present in normal cells and cancer cells, but in certain types of cancer, Myc is amplified, meaning that there are more copies of the Myc gene than there should be. In those cases, the tumor often changes and is more likely to be refractory (resistant to treatment), and more difficult to treat.

In cases of neuroblastoma without Myc-amplification, the cure rate is over 80%; however, when Myc is amplified, the cure rate drops to less than 30%. Despite intense chemotherapy and transplant procedures, the cure rate has remained unchanged for this sub-type. Dr. Graves examines the Myc gene to try to understand what it does that is different than cells with normal levels of Myc. His area of focus is on how Myc change mitochondria, a part of the cell that regulates cell death and provides cell energy. Myc changes the “stickiness” of mitochrondria, and Dr. Graves believes that by targeting a particular protein involved in mitochrondrial fusion, OPA-1, researchers may be able to target tumor cells affected by Myc-amplification. He hopes that his research will allow clinicians to target cancer cells more precisely for children with Myc-amplified neuroblastoma, providing a less toxic and more effective treatment for their disease.

Special Thanks to Our Research Partner

Hope Street Kids

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