ArticleCancers2021
Unmasking BCL-2 Addiction in Synovial Sarcoma by Overcoming Low NOXA.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03672695 (An International Phase Ib Multicentre Study to Characterize the Safety and Tolerability of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Orally Administered Venetoclax, a Selective Bcl-2 Inhibitor in Patients With Acute Myeloid Leukaemia), which is not on this map. Cited by 9 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.
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.
An International Phase Ib Multicentre Study to Characterize the Safety and Tolerability of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Orally Administered Venetoclax, a Selective Bcl-2 Inhibitor in Patients With Acute Myeloid Leukaemia (AML).
Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Oncolytic measles virotherapy encoding the neutrophil-activating protein is effective in synovial sarcoma.Molecular therapy. Oncology · 2025Article
- Targeting SUMOylation promotes cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma.Nature communications · 2025Article
- Molecular and epigenetic oncogenesis in synovial sarcoma: implications for cancer biology, diagnosis and treatment.Oncogene · 2025Review
- Current Advances and Future Strategies for BCL-2 Inhibitors: Potent Weapons against Cancers.Cancers · 2023Review
- Functional Profiling of Soft Tissue Sarcoma Using Mechanistic Models.International journal of molecular sciences · 2023Article
- Primary pleuropulmonary synovial sarcoma presenting with recurrent spontaneous pneumothorax.BMJ case reports · 2023Article
- Review
- B-cell lymphoma 2 family members and sarcomas: a promising target in a heterogeneous disease.Exploration of targeted anti-tumor therapy · 2023Review
- Specific Targeting of Antiapoptotic Bcl-2 Proteins as a Radiosensitizing Approach in Solid Tumors.International journal of molecular sciences · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
Synovial sarcoma (SS) is frequently diagnosed in teenagers and young adults and continues to be treated with polychemotherapy with variable success. The SS18-SSX gene fusion is pathognomonic for the disease, and high expression of the anti-apoptotic BCL-2 pathologically supports the diagnosis. As the oncogenic SS18-SSX fusion gene itself is not druggable, BCL-2 inhibitor-based therapies are an appealing therapeutic opportunity. Venetoclax, an FDA-approved BCL-2 inhibitor that is revolutionizing care in some BCL-2-expressing hematological cancers, affords an intriguing therapeutic possibility to treat SS. In addition, there are now dozens of venetoclax-based combination therapies in clinical trials in hematological cancers, attributing to the limited toxicity of venetoclax. However, preclinical studies of venetoclax in SS have demonstrated an unexpected ineffectiveness. In this study, we analyzed the response of SS to venetoclax and the underlying BCL-2 family biology in an effort to understand venetoclax treatment failure and find a therapeutic strategy to sensitize SS to venetoclax. We found remarkably depressed levels of the endogenous MCL-1 inhibitor, NOXA, in SS compared to other sarcomas. Expressing NOXA led to sensitization to venetoclax, as did the addition of the MCL-1 BH3 mimetic, S63845. Importantly, the venetoclax/S63845 combination induced tumor regressions in SS patient-derived xenograft (PDX) models. As a very close analog of S63845 (S64315) is now in clinical trials with venetoclax in AML (NCT03672695), the combination of MCL-1 BH3 mimetics and venetoclax should be considered for SS patients as a new therapy.
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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.