ArticleOncogene2007
KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway.
Article in Oncogene, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 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
129 citing papers in PubMed, 267 citations in OpenAlex.
- Phase II Trial of Imatinib Plus Binimetinib in Patients With Treatment-Naive Advanced Gastrointestinal Stromal Tumor.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- Precision therapeutic strategies for advanced gastrointestinal stromal tumors.Cancer metastasis reviews · 2026Review
- GALNT7 promotes the malignant progression of gastrointestinal stromal tumors by regulating KIT O-GalNAc glycosylation.Precision clinical medicine · 2026Article
- Identification of MBT3T as a new effective therapeutic option in imatinib-resistant gastrointestinal stromal tumors (GISTs).Journal of experimental & clinical cancer research : CR · 2026Article
- Golgi Retention and Oncogenic Signaling of KIT Tyrosine Kinase in Gastrointestinal Stromal Tumor.Sub-cellular biochemistry · 2026Review
- Targeted Therapy for Advanced Gastrointestinal Stromal Tumors: Evolution and Future Directions.Drug design, development and therapy · 2026Review
- The Mechanisms of Imatinib Resistance in Gastrointestinal Stromal Tumours: Theoretical Basis and Therapeutic Aspect.Journal of cellular and molecular medicine · 2025Review
- MITF regulates autophagy and extracellular vesicle cargo in gastrointestinal stromal tumors.Molecular biomedicine · 2025Article
- Golgi retention of KIT in gastrointestinal stromal tumour cells is phospholipase D activity-dependent.Scientific reports · 2025Article
- SHP2 inhibition and adjuvant therapy synergistically target KIT-mutant GISTs via ERK1/2-regulated GSK3β/cyclin D1 pathway.Clinical and translational medicine · 2025Article
- circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway.Scientific reports · 2024Article
- ONCOLINER: A new solution for monitoring, improving, and harmonizing somatic variant calling across genomic oncology centers.Cell genomics · 2024Article
- Article
- KIT mutations and expression: current knowledge and new insights for overcoming IM resistance in GIST.Cell communication and signaling : CCS · 2024Review
- KIT/PDGFRA Variant Allele Frequency as Prognostic Factor in Gastrointestinal Stromal Tumors (GISTs): Results From a Multi-Institutional Cohort Study.The oncologist · 2024Article
- Molecular Advances in the Treatment of Advanced Gastrointestinal Stromal Tumor.The oncologist · 2023Review
- G4-QuadScreen: A Computational Tool for Identifying Multi-Target-Directed Anticancer Leads against G-Quadruplex DNA.Cancers · 2023Article
- LIX1 Controls MAPK Signaling Reactivation and Contributes to GIST-T1 Cell Resistance to Imatinib.International journal of molecular sciences · 2023Article
- Review
- Identification of Thiazolo[5,4-Cancers · 2022Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most gastrointestinal stromal tumor (GIST) patients respond to KIT inhibition with imatinib, yet will eventually exhibit resistance. Imatinib-resistance mechanisms are heterogeneous, and little is known about KIT functional roles in imatinib-resistant GIST. Biological consequences of biochemical inhibition of KIT, phosphatidyl-inositol-3-kinase (PI3-K), PLCgamma, MAPK/ERK kinase/mitogen-activated protein kinase (MEK/MAPK), mammalian target of rapamycin (mTOR) and JAK were determined by immunoblotting for protein activation, and by cell proliferation and apoptosis assays in GIST cell lines from imatinib-sensitive GIST (GIST882), imatinib-resistant GISTs (GIST430 and GIST48) and KIT-negative GIST (GIST62). KIT activation was 3- to 6-fold higher in GIST430 and GIST48 than in GIST882, whereas total KIT expression was comparable in these three GIST lines. In addition to the higher set point for KIT activation, GIST430 and GIST48 had intrinsic imatinib resistance. After treatment with 1 muM imatinib, residual KIT activation was 6- and 2.8-fold higher in GIST430 and GIST48, respectively, compared to GIST882. In all GIST lines, cell growth arrest resulted from PI3-K inhibition, and - to a lesser extent - from MEK/MAPK and mTOR inhibition. Inhibition of JAK/STAT or PLCgamma did not affect cell proliferation. Similarly, only PI3-K inhibition resulted in substantial apoptosis in the imatinib-resistant GISTs. We conclude that GIST secondary KIT mutations can be associated with KIT hyperactivation and imatinib resistance. Targeting critical downstream signaling proteins, such as PI3-K, is a promising therapeutic strategy in imatinib-resistant GISTs.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.