Evidence map›Paper›PMID 41865015›Full record

ArticleJournal of experimental & clinical cancer research : CR2026

Identification of MBT3T as a new effective therapeutic option in imatinib-resistant gastrointestinal stromal tumors (GISTs).

Gloria Ravegnini, Daniele Esposito, Francesca Gorini, Tainah Dorina Marforio, Emma Coschina, Eva Benuzzi, Antonella Simone, Ahmed Samaha, Aldo Di Vito, Martina Rossi and 6 more

Abstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

16 authors.

Gloria Ravegnini *Department of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy. gloria.ravegnini2@unibo.it.ORCID http://orcid.org/0000-0002-7774-402X
Daniele Esposito *Department of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy.
Francesca Gorini *Department of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy.
Tainah Dorina MarforioDepartment of Chemistry "Giacomo Ciamician", Alma Mater Studiorum - University of Bologna, Bologna, 40126, Italy.
Emma CoschinaDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy.
Eva BenuzziDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy.
Antonella SimoneDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy.
Ahmed SamahaNeuroscience Institute, Italian Research Council (CNR), Padua, 35131, Italy.
Aldo Di VitoDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy.
Martina RossiDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy.
Patrizia HreliaDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy.
Alessandra LocatelliDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy.
Matteo CalvaresiDepartment of Chemistry "Giacomo Ciamician", Alma Mater Studiorum - University of Bologna, Bologna, 40126, Italy.
Nicola FacchinelloDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy.
Rita MorigiDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy. rita.morigi@unibo.it.
Sabrina AngeliniDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy.

Funding

Italian Ministry of Health RC-2025-2797524
6 · The paper itself

Abstract

backgroundGastrointestinal stromal tumors (GISTs) are primarily treated with tyrosine kinase inhibitors (TKIs) such as imatinib. However, the development of drug resistance remains a critical clinical challenge, highlighting the urgent need for novel therapeutic agents with alternative mechanisms of action. This study aimed to identify and characterize new small molecules effective against imatinib-sensitive and resistant GISTs.

methodsA library of 27 benzo[d]imidazo[2,1-b]thiazole derivatives was synthesized and screened for cytotoxicity against four GIST cell lines, including imatinib-sensitive (GIST-T1, GIST-882) and imatinib-resistant (GIST-48, GIST-48B) models. The most effective compound, MBT3T, was further evaluated for safety on healthy cells (PBMCs, fibroblasts) and mechanism of action using computational docking, immunofluorescence, and flow cytometry. Efficacy was validated both in 3D bioprinted tumor models and in vivo using zebrafish xenografts.

resultsMBT3T exhibited potent nanomolar cytotoxicity across all GIST cell lines while maintaining a favorable safety profile on healthy cells. Mechanistic studies revealed that MBT3T acts independently of the KIT signaling pathway, targeting tubulin at the colchicine-binding site. This interaction caused microtubule disassembly, leading to G2/M cell cycle arrest and caspase-mediated apoptosis. In in vivo zebrafish assays, MBT3T significantly reduced tumor growth in both imatinib-sensitive and resistant xenografts without inducing systemic toxicity.

conclusionWe identified MBT3T as a novel, selective tubulin polymerization inhibitor. Its ability to bypass TKIs resistance mechanisms suggests it may represent a promising therapeutic candidate for the treatment of refractory GISTs.

Indexed as

Antineoplastic AgentsDrug Resistance, NeoplasmGastrointestinal NeoplasmsGastrointestinal Stromal TumorsImatinib MesylateProtein Kinase InhibitorsAnimalsApoptosisCell Line, TumorCell ProliferationHumansMolecular Docking SimulationXenograft Model Antitumor AssaysZebrafishAntineoplastic AgentsImatinib MesylateProtein Kinase InhibitorsGISTTKI resistanceTubulin

Identifiers

PMID41865015
PMCPMC13130600

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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.