ArticleCell death & disease2020
MCL1 inhibitors S63845/MIK665 plus Navitoclax synergistically kill difficult-to-treat melanoma cells.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Cellular Senescence and Immunosenescence in Melanoma: Insights From the Tumor Microenvironment.Cancer medicine · 2025Pooled it
- The myeloid cell leukaemia-1 inhibitor MIK665 is a potent therapy in preclinical models of paediatric acute myeloid leukaemia.British journal of haematology · 2026Article
- Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.Molecules (Basel, Switzerland) · 2026Review
- MCL1 modulates mTORC1 signaling to promote bioenergetics and tumorigenesis.Nature communications · 2025Article
- Drug resistance in cancer: molecular mechanisms and emerging treatment strategies.Molecular biomedicine · 2025Review
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Targeting DNA damage in ageing: towards supercharging DNA repair.Nature reviews. Drug discovery · 2025Review
- Co-Targeting BCL-xL with MCL-1 Induces Lethal Mitochondrial Dysfunction in Diffuse Mesothelioma.Molecular cancer therapeutics · 2025Article
- Mitochondrial bioenergetics and networks in melanoma: an update.Apoptosis : an international journal on programmed cell death · 2025Review
- Targeting MCL-1 to Overcome Therapeutic Resistance and Improve Cancer Mortality.Health science reports · 2025Article
- Direct Co-Targeting of Bcl-xL and Mcl-1 Exhibits Synergistic Effects in AR-V7-Expressing CRPC Models.Cancer research communications · 2025Article
- Article
- Osteosarcoma cells depend on MCL-1 for survival, and osteosarcoma metastases respond to MCL-1 antagonism plus regorafenib in vivo.BMC cancer · 2024Article
- Disarib, a Specific BCL2 Inhibitor, Induces Apoptosis in Triple-Negative Breast Cancer Cells and Impedes Tumour Progression in Xenografts by Altering Mitochondria-Associated Processes.International journal of molecular sciences · 2024Article
- Venetoclax therapy and emerging resistance mechanisms in acute myeloid leukaemia.Cell death & disease · 2024Review
- 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
- Prognostic biomarkers for immunotherapy in esophageal cancer.Frontiers in immunology · 2024Review
- Combination of MCL-1 and BCL-2 inhibitors is a promising approach for a host-directed therapy for tuberculosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Medical Gas Plasma Technology Combines with Antimelanoma Therapies and Promotes Immune-Checkpoint Therapy Responses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
Current treatment for patients with metastatic melanoma include molecular-targeted therapies and immune checkpoint inhibitors. However, a subset of melanomas are difficult-to-treat. These melanomas include those without the genetic markers for targeted therapy, non-responsive to immunotherapy, and those who have relapsed or exhausted their therapeutic options. Therefore, it is necessary to understand and explore other biological processes that may provide new therapeutic approaches. One of most appealing is targeting the apoptotic/anti-apoptotic system that is effective against leukemia. We used genetic knockdown and pharmacologic approaches of BH3 mimetics to target anti-apoptotic BCL2 family members and identified MCL1 and BCLXL as crucial pro-survival members in melanoma. We then examined the effects of combining BH3 mimetics to target MCL1 and BCLXL in vitro and in vivo. These include clinical-trial-ready compounds such as ABT-263 (Navitoclax) and S63845/S64315 (MIK655). We used cell lines derived from patients with difficult-to-treat melanomas. In vitro, the combined inhibition of MCL1 and BCLXL resulted in significantly effective cell killing compared to single-agent treatment (p < 0.05) in multiple assays, including sphere assays. The combination-induced cell death was independent of BIM, and NOXA. Recapitulated in our mouse xenograft model, the combination inhibited tumor growth, reduced sphere-forming capacity (p < 0.01 and 0.05, respectively), and had tolerable toxicity (p > 0.40). Taken together, this study suggests that dual targeting of MCL1 and BCLXL should be considered as a treatment option for difficult-to-treat melanoma patients.
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.