What is it about?

We have discovered M606, a small molecule that fights neuroblastoma, a common childhood cancer. M606 works by removing iron from cancer cells and reducing levels of MYCN, a protein that drives tumor growth. The drug showed promise in lab tests and animal studies, offering hope for better treatments.

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Why is it important?

Our findings are significant because neuroblastoma is the most common solid tumor in young children, with poor survival rates around 50% for high-risk cases. The MYCN cancer-causing protein has been considered "undruggable" despite being a major cancer driver. M606 represents the first successful approach to directly target MYCN through iron chelation, potentially offering a less toxic alternative to current harsh treatments that cause lifelong side effects in surviving children.

Perspectives

This paper is particularly exciting for me because it demonstrates a successful strategy for targeting MYC oncoproteins using iron chelation therapy. Members of the MYC family are believed to be dysregulated in over 50% of all human cancers, however there are no clinically used drugs that directly inhibit them. Although many cancers, including neuroblastoma, have a strong dependency on iron to grow and proliferate, clinical trials using iron chelators have largely been disappointing. What makes the iron chelator that we have discovered particularly attractive is that it has a greater cell permeability so is able to more easily get inside cancer cells and reduce the levels of MYC proteins.

Murray Norris
Children's Cancer Institute Australia

Read the Original

This page is a summary of: The cell-permeable iron chelator M606 inhibits MYCN-driven neuroblastoma via an E2F3-mediated response, Proceedings of the National Academy of Sciences, June 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2420011122.
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