ArticleOncogene2018
Dual inhibition of BCL-XL and MCL-1 is required to induce tumour regression in lung squamous cell carcinomas sensitive to FGFR inhibition.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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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.
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Who cites it
50 citing papers in PubMed, 98 citations in OpenAlex.
- Elucidating molecularly stratified single agent, and combination, therapeutic strategies targeting MCL1 for lethal prostate cancer.Nature communications · 2025Article
- BCL-xL dependency in chromophobe renal cell carcinoma.Cancer gene therapy · 2025Article
- Understanding the Functional Dependence and Inhibition of the Bcl‑2 Pro-Survival Proteins in a Wide Spectrum of Cancers toward Precision Medicine.ACS pharmacology & translational science · 2025Article
- Direct Co-Targeting of Bcl-xL and Mcl-1 Exhibits Synergistic Effects in AR-V7-Expressing CRPC Models.Cancer research communications · 2025Article
- BH3 mimetics targeting BCL-XL have efficacy in solid tumors with RB1 loss and replication stress.Nature communications · 2025Article
- Integrative Multi-Omics Approaches Reveal Selectivity Profiles and Molecular Mechanisms of FIIN-2, a Covalent FGFR Inhibitor.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Both direct and indirect suppression of MCL1 synergizes with BCLXL inhibition in preclinical models of gastric cancer.Cell death & disease · 2025Article
- BCL2 expression is enriched in advanced prostate cancer with features of lineage plasticity.The Journal of clinical investigation · 2024Article
- Effective Targeting of Melanoma Cells by Combination of Mcl-1 and Bcl-2/Bcl-xInternational journal of molecular sciences · 2024Article
- BCL-XCell death & disease · 2024Article
- The identification of BCL-XL and MCL-1 as key anti-apoptotic proteins in medulloblastoma that mediate distinct roles in chemotherapy resistance.Cell death & disease · 2023Article
- Co-targeting BCL-XL and BCL-2 by PROTAC 753B eliminates leukemia cells and enhances efficacy of chemotherapy by targeting senescent cells.Haematologica · 2023Article
- Dynamic BH3 profiling identifies pro-apoptotic drug combinations for the treatment of malignant pleural mesothelioma.Nature communications · 2023Article
- Synergistic combination therapy delivered via layer-by-layer nanoparticles induces solid tumor regression of ovarian cancer.Bioengineering & translational medicine · 2023Article
- Noxa and Mcl-1 expression influence the sensitivity to BH3-mimetics that target Bcl-xL in patient-derived glioma stem cells.Scientific reports · 2022Article
- Increased apoptotic sensitivity of glioblastoma enables therapeutic targeting by BH3-mimetics.Cell death and differentiation · 2022Article
- What can we learn from mice lacking pro-survival BCL-2 proteins to advance BH3 mimetic drugs for cancer therapy?Cell death and differentiation · 2022Review
- MEK and MCL-1 sequential inhibition synergize to enhance rhabdomyosarcoma treatment.Cell death discovery · 2022Article
- Increased MCL-1 synthesis promotes irradiation-induced nasopharyngeal carcinoma radioresistance via regulation of the ROS/AKT loop.Cell death & disease · 2022Article
- Dual inhibition of anti-apoptotic proteins BCL-XL and MCL-1 enhances cytotoxicity of Nasopharyngeal carcinoma cells.Discover oncology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic alterations in the fibroblast growth factor receptors (FGFRs) have been described in multiple solid tumours including bladder cancer, head and neck and lung squamous cell carcinoma (SqCC). However, recent clinical trials showed limited efficacy of FGFR-targeted therapy in lung SqCC, suggesting combination therapy may be necessary to improve patient outcomes. Here we demonstrate that FGFR therapy primes SqCC for cell death by increasing the expression of the pro-apoptotic protein BIM. We therefore hypothesised that combining BH3-mimetics, potent inhibitors of pro-survival proteins, with FGFR-targeted therapy may enhance the killing of SqCC cells. Using patient-derived xenografts and specific inhibitors of BCL-2, BCL-XL, and MCL-1, we identified a greater reliance of lung SqCC cells on BCL-XL and MCL-1 compared to BCL-2 for survival. However, neither BCL-XL nor MCL-1 inhibitors alone provided a survival benefit in combination FGFR therapy in vivo. Only triple BCL-XL, MCL-1, and FGFR inhibition resulted in tumour volume regression and prolonged survival in vivo, demonstrating the ability of BCL-XL and MCL-1 proteins to compensate for each other in lung SqCC. Our work therefore provides a rationale for the inhibition of MCL-1, BCL-XL, and FGFR1 to maximize therapeutic response in FGFR1-expressing lung SqCC.
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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.