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Neuroblastoma Chemotherapy Resistance Linked to Transcriptional Noise in New Study

For a paper appearing in Science Advances, a research team from Australia, Belgium, and Ireland considers the roots of chemoresistance in neuroblastoma cells, focusing on transcriptional noise within a JNK apoptotic signaling network that becomes active as tumor cells succumb to treatment. By modeling single-cell JNK activity during apoptosis over time with an imaging- and biosensor-based approach, the researchers saw signs that chemotherapy resistance turns up more frequently than anticipated via random transcriptional noise and related gene expression shifts. After exploring this process further in patient-derived xenograft tumor models, the authors turned to cell line screening experiments to search for compounds to boost apoptosis when JNK pathway activity is altered, which led to a handful of chromatin-related histone deacetylase enzymes. "Promisingly, therapeutic interventions aimed at restoring JNK activity and lowering apoptotic thresholds can sensitize the JNK-impaired cells within primary tumors," they suggest, "highlighting an important option for developing more effective first-line treatment strategies."