ArticleCell death & disease2019
BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 181 citations in OpenAlex.
- Targeting protein-protein interactions in the BCL-2 family: opportunities for precision oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Disruption of MCL1/BOK transmembrane interaction as a novel strategy to induce cell death in tumours.Cell death & disease · 2026Article
- The MOGA multi-modal framework based on graph augmentation networks for drug response prediction.iScience · 2026Article
- PROTAC-mediated degradation of Bcl-xL potentiates target therapy in preclinical melanoma models.Journal of experimental & clinical cancer research : CR · 2026Article
- NovelCancer drug resistance (Alhambra, Calif.) · 2026Article
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- BCL-xL dependency in chromophobe renal cell carcinoma.Cancer gene therapy · 2025Article
- Molecular Basis of BRAF Inhibitor Resistance in Melanoma: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A new era in cancer therapy: targeting the Proteasome-Bcl-2 axis.Journal of experimental & clinical cancer research : CR · 2025Review
- Direct Co-Targeting of Bcl-xL and Mcl-1 Exhibits Synergistic Effects in AR-V7-Expressing CRPC Models.Cancer research communications · 2025Article
- Inhibition of anti-apoptotic Bcl-2 family members promotes synergistic cell death with ER stress inducers by disrupting autophagy in glioblastoma.Cell death discovery · 2025Article
- Deoxybouvardin Glucoside Induces Apoptosis in Oxaliplatin-Sensitive and -Resistant Colorectal Cancer Cells via Reactive Oxygen Species-Mediated Activation of JNK and p38 MAPK.Journal of microbiology and biotechnology · 2025Article
- Doramectin Induces Apoptosis in B16 Melanoma Cells.Anti-cancer agents in medicinal chemistry · 2025Article
- Investigating the Impact of LNA-anti-miR-92b, miR-181b, TNF-α, and Piperine on Gene Expression and Cell Viability in Jurkat Cells: Implications for Acute Lymphoblastic Leukemia : LNA-anti- MicroRNAs and Jurkat Cells.Galen medical journal · 2025Article
- Targeted Drug Nanodelivery and Immunotherapy for Combating Tumor Resistance.Combinatorial chemistry & high throughput screening · 2025Review
- Osteosarcoma cells depend on MCL-1 for survival, and osteosarcoma metastases respond to MCL-1 antagonism plus regorafenib in vivo.BMC cancer · 2024Article
- The crosstalk between non-coding RNAs and cell-cycle events: A new frontier in cancer therapy.Molecular therapy. Oncology · 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
- Immune evasion in cell-based immunotherapy: unraveling challenges and novel strategies.Journal of biomedical science · 2024Review
34 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
Abstract
Malignant melanoma is one of the most difficult cancers to treat due to its resistance to chemotherapy. Despite recent successes with BRAF inhibitors and immune checkpoint inhibitors, many patients do not respond or become resistant to these drugs. Hence, alternative treatments are still required. Due to the importance of the BCL-2-regulated apoptosis pathway in cancer development and drug resistance, it is of interest to establish which proteins are most important for melanoma cell survival, though the outcomes of previous studies have been conflicting. To conclusively address this question, we tested a panel of established and early passage patient-derived cell lines against several BH3-mimetic drugs designed to target individual or subsets of pro-survival BCL-2 proteins, alone and in combination, in both 2D and 3D cell cultures. None of the drugs demonstrated significant activity as single agents, though combinations targeting MCL-1 plus BCL-XL, and to a lesser extent BCL-2, showed considerable synergistic killing activity that was elicited via both BAX and BAK. Genetic deletion of BFL-1 in cell lines that express it at relatively high levels only had minor impact on BH3-mimetic drug sensitivity, suggesting it is not a critical pro-survival protein in melanoma. Combinations of MCL-1 inhibitors with BRAF inhibitors also caused only minimal additional melanoma cell killing over each drug alone, whilst combinations with the proteasome inhibitor bortezomib was more effective in multiple cell lines. Our data show for the first time that therapies targeting specific combinations of BCL-2 pro-survival proteins, namely MCL-1 plus BCL-XL and MCL-1 plus BCL-2, could have significant benefit for the treatment of melanoma.
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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.