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Scientists Uncover Mechanism Behind Retinoic Acid's Effectiveness in Treating Neuroblastoma

By - Dr. Bhumika Maikhuri
Published On 2025-03-04 03:00 GMT   |   Update On 2025-03-04 09:15 GMT
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Neuroblastoma is a solid tumor that occurs in children. When high-risk, the disease has a poor prognosis. Decades ago, adding the drug retinoic acid to neuroblastoma treatment increased survival by 10-15%. However, this effect was only evident in post-chemotherapy consolidation after bulky primary tumors had largely been eliminated.
A recent study has shown that retinoic acid uses a novel mechanism to kill metastasized neuroblastoma. The drug “hijacks” a normal developmental pathway to trigger cancer cell death. The findings, which have implications for future combination therapy approaches, were published in
Nature Communications.
“We’ve come up with an explanation for a decades-long contradiction about why retinoic acid works in post-chemotherapy consolidation but has little impact on primary neuroblastoma tumors,” said senior co-corresponding author Paul Geeleher, PhD, St. Jude Department of Computational Biology. “Retinoic acid’s activity heavily depends on the cellular microenvironment.
Metastasized neuroblastoma cells often migrate to bone marrow, where the
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bone morphogenetic protein (BMP) pathway signaling is highly active. The researchers showed that BMP signaling makes neuroblastoma cells much more vulnerable to retinoic acid.
Unexpectedly, we found that cells expressing genes from the BMP signaling pathway were very sensitive to retinoic acid,” said co-first and co-corresponding author Min Pan, PhD, St. Jude Department of Computational Biology. “However, since the bone marrow microenvironment causes neuroblastoma cells there to have higher BMP activity, it neatly explained why retinoic acid is very effective at treating those cells during consolidation therapy, but not the primary tumors during up-front treatment.
We found that, in neuroblastoma, BMP signaling works with retinoic acid signaling in the same way as during development,” said co-first author Yinwen Zhang, PhD, St. Jude Department of Computational Biology. Zhang characterized how transcription factors, the proteins that bind DNA to regulate gene expression, led to different results in highly retinoic acid-sensitive or insensitive neuroblastoma cells. “If there are a lot of BMP-signaling pathway transcription factors already on DNA, then retinoic acid signaling combines with it to promote downstream cell death–related gene expression. This occurs both in normal embryonic development and neuroblastoma cells in certain microenvironments.”
Ref: Pan, M., Zhang, Y., Wright, W.C. et al. Bone morphogenetic protein (BMP) signaling determines neuroblastoma cell fate and sensitivity to retinoic acid. Nat Commun 16, 2036 (2025). https://doi.org/10.1038/s41467-025-57185-y
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Article Source : Nature Communications

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Dr. Bhumika Maikhuri

Dr Bhumika Maikhuri is an orthodontist with 2 years of clinical experience. She is also working as a medical writer and anchor at Medical Dialogues. She has completed her BDS from Dr D.Y. Patil Medical College and Hospital and MDS from Kalinga Institute of Dental Sciences. She has a few publications and patents to her credit. Her diverse background in clinical dentistry and academic research uniquely positions her to contribute meaningfully to our team.

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