An irregularity within many neuroblastoma cells may indicate whether a neuroblastoma tumor, which is a type of difficult-to-treat, early childhood cancer, is vulnerable to a new class of anti-cancer drugs known as BET bromodomain inhibitors.

In studies with laboratory samples of neuroblastoma cells and mice with the disease, researchers found that tumors with excess copies, or “amplification,” of the gene MYCN were highly sensitive to BET bromodomain inhibitors. The findings may lead to clinical trials of the drugs in patients whose neuroblastoma tumors carry this amplification. This data was discussed at the annual meeting of the American Association for Cancer Research in Washington, DC, and published in Cancer Discovery (2013; doi:10.1158/2159-8290.CD-12-0418).

“BET bromodomain inhibitors are a class of drugs that, many researchers hope, may offer a new therapeutic option for treating patients with certain cancers,” said lead researcher and clinician Kimberly Stegmaier, MD, of Dana-Farber/Children’s Hospital Cancer Center in Boston, Massachusetts. “The challenge has been identifying biomarkers that can help direct clinical translation of these drugs by pinpointing those patients with the highest likelihood of response.”

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Stegmaier and her colleagues screened more than 600 cancer cell lines, each with a known set of genetic abnormalities, to see which would succumb to a prototype BET bromodomain inhibitor. They found the most susceptible cells were those with an MYCN amplification.

“Neuroblastoma is a devastating childhood cancer—the most common extracranial tumor of early childhood—and only a minority of children with aggressive forms of the disease are cured with currently available treatments,” Stegmaier remarked. “Although prior research has shown that MYCN amplification is common in neuroblastoma, it has been an elusive drug target.”

Working with Dana-Farber’s James Bradner, MD, Stegmaier found that the BET bromodomain inhibitor reduced the levels of MYCN protein in lab-grown neuroblastoma cells, resulting in impaired cell growth and induction of cell death. In studies of mice with MYCN-amplified neuroblastoma, including animals with a form of the disease that does not respond to many standard therapies, the drug had antitumor effects and prolonged survival.