ArticleCell death discovery2020
BCL-XL is an actionable target for treatment of malignant pleural mesothelioma.
Article in Cell death discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 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
15 citing papers in PubMed, 19 citations in OpenAlex.
- OT-55 reshapes tolerogenic BH3-mimetic-induced apoptosis toward immunogenic cell death in acute myeloid leukemia, potentiating PD-1/Tim-3 blockade.Cell death & disease · 2026Article
- BCL2 inhibition in acute and chronic pancreatitis - is there a therapeutic perspective?Cell death discovery · 2026Review
- Pseudo-senescence induced by palbociclib does not sensitise pleural mesothelioma cells to combinations with senolytics.Cell death & disease · 2026Article
- Targeting Bcl-xL to eliminate chemotherapy-induced tumor dormancy and prevent breast cancer metastasis.British journal of cancer · 2026Article
- Co-Targeting BCL-xL with MCL-1 Induces Lethal Mitochondrial Dysfunction in Diffuse Mesothelioma.Molecular cancer therapeutics · 2025Article
- 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
- Dynamic BH3 profiling identifies pro-apoptotic drug combinations for the treatment of malignant pleural mesothelioma.Nature communications · 2023Article
- Targeting Apoptosis in AML: Where Do We Stand?Cancers · 2022Review
- The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs.Nature reviews. Cancer · 2022Review
- Targeting the BCL-2-regulated apoptotic pathway for the treatment of solid cancers.Biochemical Society transactions · 2021Review
- Discovery, development and application of drugs targeting BCL-2 pro-survival proteins in cancer.Biochemical Society transactions · 2021Review
- Therapeutic Synergy in Esophageal Cancer and Mesothelioma Is Predicted by Dynamic BH3 Profiling.Molecular cancer therapeutics · 2021Article
- A novel BH3-mimetic, AZD0466, targeting BCL-XL and BCL-2 is effective in pre-clinical models of malignant pleural mesothelioma.Cell death discovery · 2021Article
- Malignant pleural mesothelioma co-opts BCL-XCell death & disease · 2021Article
- Co-Operativity between MYC and BCL-2 Pro-Survival Proteins in Cancer.International journal of molecular sciences · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Despite having one of the lowest survival rates of all cancers, there have been no new approved treatments for malignant pleural mesothelioma (MPM) in over a decade. Standard-of-care treatment relies on Cisplatin plus Pemetrexed chemotherapy. Here, we tested a suite of BH3-mimetic drugs targeting BCL-2 pro-survival proteins of the intrinsic apoptotic pathway. We found BCL-XL is the dominant pro-survival protein in a panel of cell lines in vitro, though potent, synergistic cell killing occurred with MCL-1 co-targeting. This correlates with high-level expression of BCL-XL and MCL-1 in cell lines and a large cohort of patient tumour samples. BCL-XL inhibition combined with Cisplatin also enhanced cell killing. In vivo BCL-XL inhibition was as effective as Cisplatin, and the combination enhanced tumour growth control and survival. Genetic ablation of MCL-1 also enhanced the effects of BCL-XL inhibitors, in vivo. Combined, these data provide a compelling rationale for the clinical investigation of BH3-mimetics targeting BCL-XL in MPM.
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.