ArticleCancers2020
Simultaneously Inhibiting BCL2 and MCL1 Is a Therapeutic Option for Patients with Advanced Melanoma.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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
21 citing papers in PubMed, 32 citations in OpenAlex.
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Molecular Basis of BRAF Inhibitor Resistance in Melanoma: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma.Cancer research · 2025Article
- Representing mutations for predicting cancer drug response.Bioinformatics (Oxford, England) · 2024Article
- Effective Targeting of Melanoma Cells by Combination of Mcl-1 and Bcl-2/Bcl-xInternational journal of molecular sciences · 2024Article
- MCL1 inhibition targets Myeloid Derived Suppressors Cells, promotes antitumor immunity and enhances the efficacy of immune checkpoint blockade.Cell death & disease · 2024Article
- Combination of MCL-1 and BCL-2 inhibitors is a promising approach for a host-directed therapy for tuberculosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Small molecules targeting protein-protein interactions for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Article
- Simultaneous Inhibition of Mcl-1 and Bcl-2 Induces Synergistic Cell Death in Hepatocellular Carcinoma.Biomedicines · 2023Article
- Targeting anti-apoptotic pathways eliminates senescent melanocytes and leads to nevi regression.Nature communications · 2022Article
- How Should the Worldwide Knowledge of Traditional Cancer Healing Be Integrated with Herbs and Mushrooms into Modern Molecular Pharmacology?Pharmaceuticals (Basel, Switzerland) · 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
- Why Senescent Cells Are Resistant to Apoptosis: An Insight for Senolytic Development.Frontiers in cell and developmental biology · 2022Review
- Tipping Growth Inhibition into Apoptosis by Combining Treatment with MDM2 and WIP1 Inhibitors in p53Cancers · 2021Article
- Inhibition of the anti-apoptotic protein MCL-1 severely suppresses human hematopoiesisHaematologica · 2021Article
- Targeting the BCL-2-regulated apoptotic pathway for the treatment of solid cancers.Biochemical Society transactions · 2021Review
- A Novel Regimen for Treating Melanoma: MCL1 Inhibitors and Azacitidine.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Targeting MCL-1 in cancer: current status and perspectives.Journal of hematology & oncology · 2021Review
- Co-Operativity between MYC and BCL-2 Pro-Survival Proteins in Cancer.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
There is an urgent need to develop treatments for patients with melanoma who are refractory to or ineligible for immune checkpoint blockade, including patients who lack BRAF-V600E/K mutations. This is often the case in patients diagnosed with rare melanoma subtypes such as mucosal and acral melanoma. Here, we analyzed data from the cutaneous melanoma The Cancer Genome Atlas Network (TCGA) transcriptomic and proteomic databases for differential expression of apoptosis molecules between melanomas with or without BRAF hotspot mutations. Our data indicated higher B-cell CLL/lymphoma 2 (BCL2) expression in melanoma without BRAF hotspot mutations, suggesting that BH3 mimetics, such as ABT-199 (venetoclax, a small molecule against BCL2), may be a potential therapeutic option for these patients. We explored the efficacy of combining two BH3 mimetics, ABT-199 and a myeloid cell leukemia sequence 1 (MCL1) inhibitor (S63845 or S64315/MIK665) in cutaneous, mucosal and acral melanomas, in vitro and in vivo. Our data indicate this combination induced cell death in a broad range of melanoma cell lines, including melanoma initiating cell populations, and was more potent in melanoma cells without BRAF-V600E/K mutations. Our knockdown/knockout experiments suggest that several pro-apoptotic BCL2 family members, BCL2-like 11 (apoptosis facilitator) (BIM), phorbol-12-myristate-13-acetate-induced protein 1 (NOXA) or BID, play a role in the combination-induced effects. Overall, our study supports the rationale for combining an MCL1 inhibitor with a BCL2 inhibitor as a therapeutic option in patients with advanced melanoma.
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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.