ArticleJournal of experimental & clinical cancer research : CR2022
The MYCN inhibitor BGA002 restores the retinoic acid response leading to differentiation or apoptosis by the mTOR block in MYCN-amplified neuroblastoma.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 23 citations in OpenAlex.
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- Advances in peptide nucleic acid for targeting RNA and genomic DNA.Cell reports. Physical science · 2026Article
- Targeting TRIM59 impairs RNA splicing and promotes neuroblastoma differentiation and therapeutic responses.Journal of experimental & clinical cancer research : CR · 2025Article
- MYC in cancer: from undruggable target to clinical trials.Nature reviews. Drug discovery · 2025Review
- Targeting Pathways in Neuroblastoma: Advances in Treatment Strategies and Clinical Outcomes.International journal of molecular sciences · 2025Review
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
- A Small Molecule Selectively Targets N-Myc to Suppress Neuroblastoma Cancer Progression.International journal of biological sciences · 2025Article
- Defining neuroblastoma: From origin to precision medicine.Neuro-oncology · 2024Review
- Recent advancements in understanding of biological role of homeobox C9 in human cancers.World journal of clinical oncology · 2024Review
- Rapamycin increases leukemia cell sensitivity to chemotherapy by regulating mTORC1 pathway-mediated apoptosis and autophagy.International journal of hematology · 2024Article
- Recent Advancements in Development and Therapeutic Applications of Genome-Targeting Triplex-Forming Oligonucleotides and Peptide Nucleic Acids.Pharmaceutics · 2023Review
- Chlorogenic Acid Induced Neuroblastoma Cells Differentiation via the ACAT1-TPK1-PDH Pathway.Pharmaceuticals (Basel, Switzerland) · 2023Article
- AntigeneCancers · 2023Article
- MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.Cancers · 2022Review
- Precision Anti-Cancer Medicines by Oligonucleotide Therapeutics in Clinical Research Targeting Undruggable Proteins and Non-Coding RNAs.Pharmaceutics · 2022Review
- Long-term survival outcomes of pediatric adrenal malignancies: An analysis with the upstaged SEER registry during 2000-2019.Frontiers in endocrinology · 2022Article
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18 authors at 4 institutions in 2 countries.
Funding
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Abstract
backgroundNeuroblastoma is a deadly childhood cancer, and MYCN-amplified neuroblastoma (MNA-NB) patients have the worst prognoses and are therapy-resistant. While retinoic acid (RA) is beneficial for some neuroblastoma patients, the cause of RA resistance is unknown. Thus, there remains a need for new therapies to treat neuroblastoma. Here we explored the possibility of combining a MYCN-specific antigene oligonucleotide BGA002 and RA as therapeutic approach to restore sensitivity to RA in NB.
methodsBy molecular and cellular biology techniques, we assessed the combined effect of the two compounds in NB cell lines and in a xenograft mouse model MNA-NB.
resultsWe found that MYCN-specific inhibition by BGA002 in combination with RA (BGA002-RA) act synergistically and overcame resistance in NB cell lines. BGA002-RA also reactivated neuron differentiation (or led to apoptosis) and inhibited invasiveness capacity in MNA-NB. Moreover, we found that neuroblastoma had the highest level of mRNA expression of mTOR pathway genes, and that BGA002 led to mTOR pathway inhibition followed by autophagy reactivation in MNA-NB cells, which was strengthened by BGA002-RA. BGA002-RA in vivo treatment also eliminated tumor vascularization in a MNA-NB mouse model and significantly increased survival.
conclusionTaken together, MYCN modulation mediates the therapeutic efficacy of RA and the development of RA resistance in MNA-NB. Furthermore, by targeting MYCN, a cancer-specific mTOR pathway inhibition occurs only in MNA-NB, thus avoiding the side effects of targeting mTOR in normal cells. These findings warrant clinical testing of BGA002-RA as a strategy for overcoming RA resistance in MNA-NB.
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