ArticlePloS one2011
The combination of BH3-mimetic ABT-737 with the alkylating agent temozolomide induces strong synergistic killing of melanoma cells independent of p53.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- miR in melanoma development: miRNAs and acquired hallmarks of cancer in melanoma.Physiological genomics · 2013Pooled it
- Characterization of coagulation-related gene signature to predict prognosis and tumor immune microenvironment in skin cutaneous melanoma.Frontiers in oncology · 2022Article
- Interleukin enhancer-binding factor 2 promotes cell proliferation and DNA damage response in metastatic melanoma.Clinical and translational medicine · 2021Article
- A Novel Regimen for Treating Melanoma: MCL1 Inhibitors and Azacitidine.Pharmaceuticals (Basel, Switzerland) · 2021Article
- NBM-BMX, an HDAC8 Inhibitor, Overcomes Temozolomide Resistance in Glioblastoma Multiforme by Downregulating the β-Catenin/c-Myc/SOX2 Pathway and Upregulating p53-Mediated MGMT Inhibition.International journal of molecular sciences · 2021Article
- Temozolomide: An Updated Overview of Resistance Mechanisms, Nanotechnology Advances and Clinical Applications.Current neuropharmacology · 2021Review
- Simultaneously Inhibiting BCL2 and MCL1 Is a Therapeutic Option for Patients with Advanced Melanoma.Cancers · 2020Article
- MCL1 inhibitors S63845/MIK665 plus Navitoclax synergistically kill difficult-to-treat melanoma cells.Cell death & disease · 2020Article
- BH3 mimetics induce apoptosis independent of DRP-1 in melanoma.Cell death & disease · 2018Article
- Licochalcone D induces apoptosis and inhibits migration and invasion in human melanoma A375 cells.Oncology reports · 2018Article
- Solid Lipid Nanoparticles Carrying Temozolomide for Melanoma Treatment. Preliminary In Vitro and In Vivo Studies.International journal of molecular sciences · 2018Article
- Bcl‑2 associated athanogene 4 promotes proliferation, migration and invasion of gastric cancer cells.Molecular medicine reports · 2017Article
- Use of a MCL-1 inhibitor alone to de-bulk melanoma and in combination to kill melanoma initiating cells.Oncotarget · 2017Article
- Upregulation of CYP17A1 by Sp1-mediated DNA demethylation confers temozolomide resistance through DHEA-mediated protection in glioma.Oncogenesis · 2017Article
- Combining a GSI and BCL-2 inhibitor to overcome melanoma's resistance to current treatments.Oncotarget · 2016Article
- Restraining FOXO3-dependent transcriptional BMF activation underpins tumour growth and metastasis of E-cadherin-negative breast cancer.Cell death and differentiation · 2016Article
- Preferential targeting of cancer stem cells in the radiosensitizing effect of ABT-737 on HNSCC.Oncotarget · 2016Article
- Alternative Treatments For Melanoma: Targeting BCL-2 Family Members to De-Bulk and Kill Cancer Stem Cells.The Journal of investigative dermatology · 2015Review
- A transcriptomic signature mediated by HOXA9 promotes human glioblastoma initiation, aggressiveness and resistance to temozolomide.Oncotarget · 2015Article
- Combining a BCL2 inhibitor with the retinoid derivative fenretinide targets melanoma cells including melanoma initiating cells.The Journal of investigative dermatology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Metastatic melanoma has poor prognosis and is refractory to most conventional chemotherapies. The alkylating agent temozolomide (TMZ) is commonly used in treating melanoma but has a disappointing response rate. Agents that can act cooperatively with TMZ and improve its efficacy are thus highly sought after. The BH3 mimetic ABT-737, which can induce apoptosis by targeting pro-survival Bcl-2 family members, has been found to enhance the efficacy of many conventional chemotherapeutic agents in multiple cancers. We found that combining TMZ and ABT-737 induced strong synergistic apoptosis in multiple human melanoma cell lines. When the drugs were used in combination in a mouse xenograft model, they drastically reduced tumor growth at concentrations where each individual drug had no significant effect. We found that TMZ treatment elevated p53 levels, and that the pro-apoptotic protein Noxa was elevated in TMZ/ABT-737 treated cells. Experiments with shRNA demonstrated that the synergistic effect of TMZ and ABT-737 was largely dependent on Noxa. Experiments with nutlin-3, a p53 inducer, demonstrated that p53 induction was sufficient for synergistic cell death with ABT-737 in a Noxa-dependent fashion. However, p53 was not necessary for TMZ/ABT-737 synergy as demonstrated by a p53-null line, indicating that TMZ and ABT-737 together induce Noxa in a p53-independent fashion. These results demonstrate that targeting anti-apoptotic Bcl-2 members is a promising method for treating metastatic melanoma, and that clinical trials with TMZ and Bcl-2 inhibitors are warranted.
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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.