ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
A PDE3A-SLFN12 Molecular Glue Exhibits Significant Antitumor Activity in TKI-Resistant Gastrointestinal Stromal Tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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.
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
8 citing papers in PubMed.
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Preclinical response of uveal melanomas to the velcrin compound, BAY 2666605.Molecular cancer therapeutics · 2026Article
- Pan-cancer ex vivo target evaluation of phosphodiesterase 3 A (PDE3A).Journal of molecular medicine (Berlin, Germany) · 2026Article
- The Role of PDE3A in Cancer.ACS omega · 2026Review
- Schlafen 12 Modulation and Targeting in Acute Myeloid Leukemia.Cancer research communications · 2025Article
- Phosphodiesterase 3 A expression in gastrointestinal stromal tumors.Virchows Archiv : an international journal of pathology · 2025Article
- First-in-Human Dose-Escalation Study of the First-in-Class PDE3A-SLFN12 Complex Inducer BAY 2666605 in Patients with Advanced Solid Tumors Coexpressing SLFN12 and PDE3A.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Discovery of BAY 2666605, a Molecular Glue for PDE3A and SLFN12.ACS medicinal chemistry letters · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeGastrointestinal stromal tumor (GIST), the most common mesenchymal tumor with KIT or PDGFRA driver mutations, is typically treated with tyrosine kinase inhibitors (TKI). However, resistance to TKIs due to secondary mutations is a common challenge in advanced GISTs. In addition, there are currently no effective therapies for several other molecular subtypes, such as succinate dehydrogenase-deficient GISTs. Therefore, novel therapeutic strategies are needed. EXPERIMENTAL
designTo address this need, we tested the efficacy of a novel non-TKI compound, OPB-171775, using patient-derived xenograft models of GISTs. In parallel, we sought to elucidate the mechanism of action of the compound.
resultsOur study revealed that OPB-171775 exhibited significant efficacy against GISTs regardless of their KIT mutation status by inducing complex formation between phosphodiesterase 3A (PDE3A) and Schlafen family member 12 (SLFN12), which are highly expressed in GISTs, leading to SLFN12 RNase-mediated cell death. Furthermore, we identified the activation of general control non-derepressible 2 and its downstream response as an effector pathway of SLFN12 in mediating anticancer activity and revealed potential pharmacodynamic markers.
conclusionsThese findings suggest that OPB-171775, with its significant efficacy, could potentially serve as a novel and effective treatment option for advanced GISTs, particularly those resistant to TKIs.
Indexed as
Identifiers
What Socratic 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 Socratic graph.