ArticleMolecular cancer therapeutics2019
Fenretinide via NOXA Induction, Enhanced Activity of the BCL-2 Inhibitor Venetoclax in High BCL-2-Expressing Neuroblastoma Preclinical Models.
Article in Molecular cancer therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Fenretinide in cancer therapy and chemoprevention: past, present and future.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Drug Resistance: The Role of Sphingolipid Metabolism.International journal of molecular sciences · 2025Review
- Synergy of retinoic acid and BH3 mimetics in MYC(N)-driven embryonal nervous system tumours.British journal of cancer · 2024Article
- NanoacetylatedACS medicinal chemistry letters · 2022Article
- Targeting the apoptosis pathway to treat tumours of the paediatric nervous system.Cell death & disease · 2022Review
- Patient-derived models: Advanced tools for precision medicine in neuroblastoma.Frontiers in oncology · 2022Review
- Probenecid increases renal retention and antitumor activity of DFMO in neuroblastoma.Cancer chemotherapy and pharmacology · 2021Article
- ALT neuroblastoma chemoresistance due to telomere dysfunction-induced ATM activation is reversible with ATM inhibitor AZD0156.Science translational medicine · 2021Article
- Programmed cell death, redox imbalance, and cancer therapeutics.Apoptosis : an international journal on programmed cell death · 2021Review
- A phase I study of intravenous fenretinide (4-HPR) for patients with malignant solid tumors.Cancer chemotherapy and pharmacology · 2021Article
- Catastrophic ATP loss underlies a metabolic combination therapy tailored forProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Targeting the Integrated Stress Response in Cancer Therapy.Frontiers in pharmacology · 2021Review
- Targeting Sphingolipids for Cancer Therapy.Frontiers in oncology · 2021Review
- ATF3 Coordinates Antitumor Synergy between Epigenetic Drugs and Protein Disulfide Isomerase Inhibitors.Cancer research · 2020Article
- Article
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8 authors.
Funding
Abstract
Recurrent high-risk neuroblastoma is a childhood cancer that often fails to respond to therapy. Fenretinide (4-HPR) is a cytotoxic retinoid with clinical activity in recurrent neuroblastoma and venetoclax (ABT-199) is a selective inhibitor of the antiapoptotic protein B-cell lymphoma-2 (BCL-2). We evaluated activity of 4-HPR + ABT-199 in preclinical models of neuroblastoma. Patient-derived cell lines and xenografts from progressive neuroblastoma were tested. Cytotoxicity was evaluated by DIMSCAN, apoptosis by flow cytometry, and gene expression by RNA sequencing, quantitative RT-PCR, and immunoblotting. 4-HPR + ABT-199 was highly synergistic against high BCL-2-expressing neuroblastoma cell lines and significantly improved event-free survival of mice carrying high BCL-2-expressing patient-derived xenografts (PDX). In 10 matched-pair cell lines [established at diagnosis (DX) and progressive disease (PD) from the same patients], BCL-2 expression in the DX and PD lines was comparable, suggesting that BCL-2 expression at diagnosis may provide a biomarker for neuroblastomas likely to respond to 4-HPR + ABT-199. In a pair of DX (COG-N-603x) and PD (COG-N-623x) PDXs established from the same patient, COG-N-623x was less responsive to cyclophosphamide + topotecan than COG-N-603x, but both DX and PD PDXs were responsive to 4-HPR + ABT-199. Synergy of 4-HPR + ABT-199 was mediated by induction of NOXA via 4-HPR stimulation of reactive oxygen species that induced expression of ATF4 and ATF3, transcription factors for NOXA. Thus, fenretinide + venetoclax is a synergistic combination that warrants clinical testing in high BCL-2-expressing neuroblastoma.
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