New Findings on Neuroblastoma: Oncogene Position Influences Treatment Resistance

Researchers have made significant strides in understanding neuroblastoma, a challenging pediatric cancer that affects children primarily under the age of five. Neuroblastoma tumors originate from the sympathetic nervous system and display a wide range of behaviors, with some cases regressing without treatment while others progress aggressively.

A major contributing factor to this aggressiveness is the oncogene MYCN, which is often found in elevated copies within tumor cells. A research team from the Experimental and Clinical Research Center (ECRC), part of Charité--Universitätsmedizin Berlin and the Max Delbrück Center, has discovered that the genomic location of the MYCN gene is critical in determining the aggressiveness of neuroblastoma.

The study indicates that when MYCN is positioned outside of chromosomes, cancer cells can enter a dormant state, thus evading conventional therapies. This finding was detailed in a recent publication in the journal Cancer Discovery, where the team outlined a novel therapeutic approach that targets these dormant cells. Initial experiments in mouse models have shown promising results, suggesting a new direction for treatment.

In exploring the behavior of MYCN, researchers found that neuroblastoma cells with high copies of the gene are typically more susceptible to chemotherapy. Conversely, those with fewer copies enter a dormant state, described as a 'deep sleep,' allowing them to survive treatment and potentially lead to cancer recurrence.

The research team, led by Dr. Jan Dörr and Professor Anton Henssen, emphasized the importance of international collaboration in advancing cancer research. They utilized advanced methodologies to separate and analyze tumor cells based on MYCN copy numbers, which revealed significant differences in protein composition and cell behavior.

Dr. Dörr noted that combining chemotherapy with agents designed to awaken these dormant cells could enhance treatment efficacy, particularly in cases where MYCN is present on extrachromosomal DNA. This strategy may also be applicable to other cancers with similar genomic characteristics.

The next steps for this research team involve identifying additional compounds that can specifically target dormant tumor cells while sparing healthy tissue. This approach holds promise not only for neuroblastoma but also for other malignancies associated with extrachromosomal oncogenes, including certain brain tumors.