One gene marker predicts childhood cancer survival
In childhood cancer, predicting who responds well to treatment and who does not is critical. A new study identifies a gene that predicts five-year survival in a common childhood tumor, and in doing so also exposes a mechanism relevant to aging.
Researchers studied neuroblastoma, a malignant tumor arising from nerve cells that predominantly affects young children. They discovered how a regulatory factor in the cell nucleus (the transcription factor FOXC1) drives expression of the gene ARHGAP36. That gene inhibits an enzyme (protein kinase A, or PKA) that normally suppresses a growth signaling pathway called the Hedgehog pathway. When FOXC1 activates ARHGAP36, PKA is blocked and the Hedgehog pathway becomes overactive. This makes tumor cells more aggressive and resistant to certain drugs. The study was published in the journal eLife.
What the clinical data show
The researchers validated their findings in a cohort of 1,348 neuroblastoma patients. Higher ARHGAP36 expression was associated with better five-year survival. That appears paradoxical: the gene that drives tumor growth correlates with a better outcome? The explanation likely lies in context: ARHGAP36 is tissue-specific and its effects depend on other cellular factors.
For diagnostics, this is promising. A marker that predicts survival helps clinicians make better-informed treatment decisions. Whether it also represents a therapeutic target requires further investigation.
The link to aging and cancer
From a broader perspective, it is notable that the same signaling pathways disrupted in neuroblastoma also play a role in normal cell renewal and aging. The Hedgehog pathway regulates cell renewal in multiple tissues. When that pathway is chronically overactive (which can occur in later life through other mechanisms), it increases the risk of malignant cell division. The mechanisms unraveled in this pediatric cancer study may therefore also shed light on aging-related tumor development in adults.
Search terms to explore further: Hedgehog signaling pathway tumor development, protein kinase A cell cycle regulation, FOXC1 transcription factor cancer prognosis