ArticleOncotarget2016
Combining a GSI and BCL-2 inhibitor to overcome melanoma's resistance to current treatments.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Pooled it
- Head and neck squamous cell carcinoma: current and emerging therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024Review
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- MCL1 inhibition targets Myeloid Derived Suppressors Cells, promotes antitumor immunity and enhances the efficacy of immune checkpoint blockade.Cell death & disease · 2024Article
- Uncovering NOTCH1 as a Promising Target in the Treatment ofInternational journal of molecular sciences · 2023Article
- Therapeutic Targeting of Regulated Signaling Pathways of Non-Small Cell Lung Carcinoma.ACS omega · 2023Review
- Review
- Current Landscape of Therapeutic Resistance in Lung Cancer and Promising Strategies to Overcome Resistance.Cancers · 2022Review
- Expression Differences in BCL2 Family Members between Uveal and Cutaneous Melanomas Account for Varying Sensitivity to BH3 Mimetics.The Journal of investigative dermatology · 2022Article
- The Interplay between Tumour Microenvironment Components in Malignant Melanoma.Medicina (Kaunas, Lithuania) · 2022Review
- Bax/Bcl-2 Cascade Is Regulated by the EGFR Pathway: Therapeutic Targeting of Non-Small Cell Lung Cancer.Frontiers in oncology · 2022Review
- Review
- A Novel Regimen for Treating Melanoma: MCL1 Inhibitors and Azacitidine.Pharmaceuticals (Basel, Switzerland) · 2021Article
- The Role of Senescent Cells in Acquired Drug Resistance and Secondary Cancer in BRAFi-Treated Melanoma.Cancers · 2021Review
- Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy.Molecules (Basel, Switzerland) · 2021Review
- Oral Cancer Stem Cells: Therapeutic Implications and Challenges.Frontiers in oral health · 2021Review
- Enrichment of Melanoma Stem-Like Cells via Sphere Assays.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Review
- Simultaneously Inhibiting BCL2 and MCL1 Is a Therapeutic Option for Patients with Advanced Melanoma.Cancers · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Major limitations of current melanoma treatments are for instances of relapse and the lack of therapeutic options for BRAF wild-type patients who do not respond to immunotherapy. Many studies therefore focus on killing resistant subpopulations, such as Melanoma Initiating Cells (MICs) to prevent relapse. Here we examined whether combining a GSI (γ-Secretase Inhibitor) with ABT-737 (a small molecule BCL-2/BCL-XL/BCL-W inhibitor) can kill both the non-MICs (bulk of melanoma) and MICs. To address the limitations of melanoma therapies, we included multiple tumor samples of patients relapsed from current treatments, with a diverse genetic background (with or without the common BRAF, NRAS or NF1 mutations) in these studies. Excitingly, the combination treatment reduced cell viability and induced apoptosis of the non-MICs; disrupted primary spheres, decreased the ALDH+ cells, and inhibited the self-renewability of the MICs in multiple melanoma cell lines and relapsed patient samples. Using a low-cell-number mouse xenograft model, we demonstrated that the combination significantly reduced the tumor initiating ability of MIC-enriched cultures from relapsed patient samples. Mechanistic studies also indicate that cell death is NOXA-dependent. In summary, this combination may be a promising strategy to address treatment relapse and for triple wild-type patients who do not respond to immunotherapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.