ArticleThe Journal of investigative dermatology2015
Combining a BCL2 inhibitor with the retinoid derivative fenretinide targets melanoma cells including melanoma initiating cells.
Article in The Journal of investigative dermatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- MCL1 inhibition targets Myeloid Derived Suppressors Cells, promotes antitumor immunity and enhances the efficacy of immune checkpoint blockade.Cell death & disease · 2024Article
- Expression Differences in BCL2 Family Members between Uveal and Cutaneous Melanomas Account for Varying Sensitivity to BH3 Mimetics.The Journal of investigative dermatology · 2022Article
- A Novel Regimen for Treating Melanoma: MCL1 Inhibitors and Azacitidine.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Enrichment of Melanoma Stem-Like Cells via Sphere Assays.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Simultaneously Inhibiting BCL2 and MCL1 Is a Therapeutic Option for Patients with Advanced Melanoma.Cancers · 2020Article
- MCL1 inhibitors S63845/MIK665 plus Navitoclax synergistically kill difficult-to-treat melanoma cells.Cell death & disease · 2020Article
- Nanomicellar Lenalidomide-Fenretinide Combination Suppresses Tumor Growth in anInternational journal of nanomedicine · 2020Article
- A novel oral micellar fenretinide formulation with enhanced bioavailability and antitumour activity against multiple tumours from cancer stem cells.Journal of experimental & clinical cancer research : CR · 2019Article
- A Novel Nanomicellar Combination of Fenretinide and Lenalidomide Shows Marked Antitumor Activity in a Neuroblastoma Xenograft Model.Drug design, development and therapy · 2019Article
- BH3 mimetics induce apoptosis independent of DRP-1 in melanoma.Cell death & disease · 2018Article
- CPP-E1A fusion peptides inhibit CtBP-mediated transcriptional repression.Molecular oncology · 2018Article
- p53-independent Noxa induction by cisplatin is regulated by ATF3/ATF4 in head and neck squamous cell carcinoma cells.Molecular oncology · 2018Article
- Use of a MCL-1 inhibitor alone to de-bulk melanoma and in combination to kill melanoma initiating cells.Oncotarget · 2017Article
- Therapeutic implications of cellular and molecular biology of cancer stem cells in melanoma.Molecular cancer · 2017Review
- Combining a GSI and BCL-2 inhibitor to overcome melanoma's resistance to current treatments.Oncotarget · 2016Article
- IGF-1 contributes to the expansion of melanoma-initiating cells through an epithelial-mesenchymal transition process.Oncotarget · 2016Article
- Restraining FOXO3-dependent transcriptional BMF activation underpins tumour growth and metastasis of E-cadherin-negative breast cancer.Cell death and differentiation · 2016Article
- Fenretinide: A Potential Treatment for Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2016Article
- Resistance to Cell Death and Its Modulation in Cancer Stem Cells.Critical reviews in oncogenesis · 2016Review
- TIC10/ONC201 synergizes with Bcl-2/Bcl-xL inhibition in glioblastoma by suppression of Mcl-1 and its binding partners in vitro and in vivo.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Investigations from multiple laboratories support the existence of melanoma initiating cells (MICs) that potentially contribute to melanoma's drug resistance. ABT-737, a small molecule BCL-2/BCL-XL/BCL-W inhibitor, is promising in cancer treatments, but not very effective against melanoma, with the antiapoptotic protein MCL-1 as the main contributor to resistance. The synthetic retinoid fenretinide N-(4-hydroxyphenyl)retinamide (4-HPR) has shown promise for treating breast cancers. Here, we tested whether the combination of ABT-737 with 4-HPR is effective in killing both the bulk of melanoma cells and MICs. The combination synergistically decreased cell viability and caused cell death in multiple melanoma cells lines (carrying either BRAF or NRAS mutations) but not in normal melanocytes. The combination increased the NOXA expression and caspase-dependent MCL-1 degradation. Knocking down NOXA protected cells from combination-induced apoptosis, implicating the role of NOXA in the drug synergy. The combination treatment also disrupted primary spheres (a functional assay for MICs) and decreased the percentage of aldehyde dehydrogenase (high) cells (a marker of MICs) in melanoma cell lines. Moreover, the combination inhibited the self-renewal capacity of MICs, measured by secondary sphere-forming assays. In vivo, the combination inhibited tumor growth. Thus, this combination is a promising treatment strategy for melanoma, regardless of mutation status of BRAF or NRAS.
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