New research published in the journal Cancer Research describes the process by which iron can trigger cell death in neuroblastoma cancer cells. The findings have implications for the development of future drugs that target the MYCN gene, which is overexpressed in 20-25% of neuroblastoma.
Neuroblastoma is a cancer of the nerve tissue seen most commonly in the glands around the kidneys. It affects mostly children ages five or younger. Researchers from VCU Massey Cancer Center are investigating how the MYCN gene is influenced by iron levels that cause ferroptosis, or cell death by way of iron accumulation.
"Iron is a double-edged sword in a cancer cell. It can help the cancer grow and survive, but it also creates these toxic molecules within the cell called reactive oxygen species," said Anthony Faber, Ph.D., who is an associate professor in the Philips Institute for Oral Health Research at the VCU School of Dentistry.
Due to their chemical instability, reactive oxygen species damage genes and can trigger cell death. Ferroptosis is one such form of cell death, but the scientific community is still trying to figure how to harness this iron-induced cell death for our benefit. The key to this is understanding how MYCN works.
"As MYCN continues to be one of the most important targets in cancer therapeutics, this study highlights a new and clinically important strategy for treating MYCN-associated cancers," Faber explained.
The scientists found that the MYCN gene is susceptible to drugs that induce ferroptosis because MYCN requires large amounts of iron to promote the cancer cell’s growth. The team plans to test the ability of FDA-approved drugs sulfasalazine and auronofin to induce ferroptosis and tumor responses in MYCN-amplified neuroblastoma cells.
The team will first test the drugs in patient-derived models and orthotopic models before moving on to clinical trials.