ArticleOncotarget2015
The splicing modulator sudemycin induces a specific antitumor response and cooperates with ibrutinib in chronic lymphocytic leukemia.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
- Evaluating splicing factor and kinase network crosstalk through global phosphoproteomics.bioRxiv : the preprint server for biology · 2026Article
- Advancing the therapeutic effectiveness of paclitaxel in chronic lymphocytic leukemia through the simultaneous inhibition of NOTCH1 and SF3B1.Cancer cell international · 2025Article
- Tipping the balance of cell death: alternative splicing as a source of MCL-1S in cancer.Cell death & disease · 2024Review
- Targeting splicing for hematological malignancies therapy.BMC genomics · 2024Review
- Article
- Exploring Splicing Modulation as an Innovative Approach to Combat Pancreatic Cancer: SF3B1 Emerges as a Prognostic Indicator and Therapeutic Target.International journal of biological sciences · 2024Article
- Article
- The role of alternative pre-mRNA splicing in cancer progression.Cancer cell international · 2023Review
- Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects.Nature reviews. Genetics · 2023Review
- Review
- Molecular mechanisms by which splice modulator GEX1A inhibits leukaemia development and progression.British journal of cancer · 2022Article
- The "Janus-like" RNA-editing machinery in innate antiviral immunity.Current trends in immunology · 2022Article
- Perspectives on Precision Medicine in Chronic Lymphocytic Leukemia: Targeting Recurrent Mutations-NOTCH1, SF3B1, MYD88, BIRC3.Journal of clinical medicine · 2021Review
- A synthetic small molecule stalls pre-mRNA splicing by promoting an early-stage U2AF2-RNA complex.Cell chemical biology · 2021Article
- Challenges with Approved Targeted Therapies against Recurrent Mutations in CLL: A Place for New Actionable Targets.Cancers · 2021Review
- SF3B1 modulators affect key genes in metastasis and drug influx: a new approach to fight pancreatic cancer chemoresistance.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Roles and mechanisms of alternative splicing in cancer - implications for care.Nature reviews. Clinical oncology · 2020Review
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- Apoptosis induction and cell cycle arrest of pladienolide B in erythroleukemia cell lines.Investigational new drugs · 2020Article
- Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutations or deregulated expression of the components of the spliceosome can influence the splicing pattern of several genes and contribute to the development of tumors. In this context, we report that the spliceosome modulator sudemycin induces selective cytotoxicity in primary chronic lymphocytic leukemia (CLL) cells when compared with healthy lymphocytes and tumor cells from other B-lymphoid malignancies, with a slight bias for CLL cases with mutations in spliceosome-RNA processing machinery. Consistently, sudemycin exhibits considerable antitumor activity in NOD/SCID/IL2Rγ-/- (NSG) mice engrafted with primary cells from CLL patients. The antileukemic effect of sudemycin involves the splicing modulation of several target genes important for tumor survival, both in SF3B1-mutated and -unmutated cases. Thus, the apoptosis induced by this compound is related to the alternative splicing switch of MCL1 toward its proapoptotic isoform. Sudemycin also functionally disturbs NF-κB pathway in parallel with the induction of a spliced RELA variant that loses its DNA binding domain. Importantly, we show an enhanced antitumor effect of sudemycin in combination with ibrutinib that might be related to the modulation of the alternative splicing of the inhibitor of Btk (IBTK). In conclusion, we provide first evidence that the spliceosome is a relevant therapeutic target in CLL, supporting the use of splicing modulators alone or in combination with ibrutinib as a promising approach for the treatment of CLL patients.
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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.