Evidence map›Paper›PMID 30635584›Full record

ArticleNature communications2019

Sensitivity to splicing modulation of BCL2 family genes defines cancer therapeutic strategies for splicing modulators.

Daniel Aird, Teng Teng, Chia-Ling Huang, Ermira Pazolli, Deepti Banka, Kahlin Cheung-Ong, Cheryl Eifert, Craig Furman, Zhenhua Jeremy Wu, Michael Seiler and 12 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 72 citations in OpenAlex.

  1. RNA splicing in health and disease.Molecular biomedicine · 2026
    Review
  2. Article
  3. Article
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  5. Article
  6. Article
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  8. BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025
    Review
  16. Review
  17. Life science alliance · 2023
    Article
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 1 institution in 1 country.

Daniel AirdH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Teng TengH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Chia-Ling HuangH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Ermira PazolliH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Deepti BankaH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Kahlin Cheung-OngH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Cheryl EifertH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Craig FurmanH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Zhenhua Jeremy WuH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Michael SeilerH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Silvia BuonamiciH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Peter FekkesH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Craig KarrH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
James PalacinoH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0003-4590-7290
Eunice ParkH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Peter G SmithH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Lihua YuH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Yoshiharu MizuiH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Markus WarmuthH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Agustin ChicasH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Laura CorsonH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.
Ping ZhuH3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA. ping_zhu@h3biomedicine.com.
Cellular Biomedicine Group (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysregulation of RNA splicing by spliceosome mutations or in cancer genes is increasingly recognized as a hallmark of cancer. Small molecule splicing modulators have been introduced into clinical trials to treat solid tumors or leukemia bearing recurrent spliceosome mutations. Nevertheless, further investigation of the molecular mechanisms that may enlighten therapeutic strategies for splicing modulators is highly desired. Here, using unbiased functional approaches, we report that the sensitivity to splicing modulation of the anti-apoptotic BCL2 family genes is a key mechanism underlying preferential cytotoxicity induced by the SF3b-targeting splicing modulator E7107. While BCL2A1, BCL2L2 and MCL1 are prone to splicing perturbation, BCL2L1 exhibits resistance to E7107-induced splicing modulation. Consequently, E7107 selectively induces apoptosis in BCL2A1-dependent melanoma cells and MCL1-dependent NSCLC cells. Furthermore, combination of BCLxL (BCL2L1-encoded) inhibitors and E7107 remarkably enhances cytotoxicity in cancer cells. These findings inform mechanism-based approaches to the future clinical development of splicing modulators in cancer treatment.

Indexed as

A549 CellsAnimalsAntineoplastic AgentsApoptosisApoptosis Regulatory Proteinsbcl-X ProteinCarcinoma, Non-Small-Cell LungCell Line, TumorDoxycyclineDrug SynergismEpoxy CompoundsExome SequencingFemaleHumansLung NeoplasmsMacrolidesAntineoplastic AgentsApoptosis Regulatory ProteinsBCL2L1 protein, humanBCL2L2 protein, humanBCL2-related protein A1bcl-X ProteinDoxycyclineE 7107Epoxy CompoundsMacrolidesMCL1 protein, humanMinor Histocompatibility AntigensMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-bcl-2RNA, Small Interfering

Identifiers

PMID30635584
PMCPMC6329755
OpenAlexW2914370117

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.