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Biological Chemistry

New Strategy For Stubborn Neuroblastomas

Medicinal Chemistry: Analysis of gene expression in patient tumors reveals novel target for aggressive, resistant forms of the disease

by Michael Torrice
November 9, 2015 | APPEARED IN VOLUME 93, ISSUE 44

Neuroblastoma, a type of childhood cancer that develops in immature nerve cells, can become aggressive, acquiring resistance to standard chemotherapy drugs. Now, researchers report a novel target for attacking these resistant tumors (Sci. Transl. Med. 2015, DOI: 10.1126/scitranslmed.aab1803). Aggressive neuroblastomas often have multiple copies of a gene called MYCN, which codes for a protein that controls the expression of other genes. Through an analysis of genes expressed in association with MYCN in tumors from 649 neuroblastoma patients, a team led by Glenn M. Marshall and Michelle Haber of the University of New South Wales zeroed in on a gene coding for a protein complex called FACT. The researchers determined that when MYCN triggers expression of this protein, FACT turns around and helps increase MYCN’s expression. Inhibiting FACT with CBL0137, a compound already in clinical trials for other types of cancer, shut down this feedback loop and slowed tumor growth in mice. The compound was even more potent when paired with conventional chemotherapy drugs, such as cisplatin, suggesting that a combination therapy involving CBL0137 could be effective against resistant neuroblastomas.

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