ArticleCancers2021
Antitumoral Activity of the MEK Inhibitor Trametinib (TMT212) Alone and in Combination with the CDK4/6 Inhibitor Ribociclib (LEE011) in Neuroendocrine Tumor Cells In Vitro.
Article in Cancers, 2021. 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
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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
8 citing papers in PubMed, 7 citations in OpenAlex.
- Prognostic and therapeutic roles of specific genotypes through target-gene sequencing on gastroenteropancreatic neuroendocrine carcinoma.The oncologist · 2026Article
- Diagnostic significance of the checkpoint kinase 1 gene in high-grade gastroenteropancreatic neuroendocrine neoplasms.Experimental and therapeutic medicine · 2026Article
- New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic.Research (Washington, D.C.) · 2025Review
- Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer.International journal of molecular sciences · 2023Review
- MEK inhibition causes BIM stabilization and increased sensitivity to BCL-2 family member inhibitors in RAS-MAPK-mutated neuroblastoma.Frontiers in oncology · 2023Article
- Genomic characterization reveals distinct mutation landscapes and therapeutic implications in neuroendocrine carcinomas of the gastrointestinal tract.Cancer communications (London, England) · 2022Article
- Direct Targeting of the Raf-MEK-ERK Signaling Cascade Inhibits Neuroblastoma Growth.Current oncology (Toronto, Ont.) · 2022Article
- Cyclin-dependent Kinases 4/6 Inhibitors in Neuroendocrine Neoplasms: from Bench to Bedside.Current oncology reports · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThis study assessed the antitumoral activity of the MEK inhibitor trametinib (TMT212) and the ERK1/2 inhibitor SCH772984, alone and in combination with the CDK4/6 inhibitor ribociclib (LEE011) in human neuroendocrine tumor (NET) cell lines in vitro.
methodsHuman NET cell lines BON1, QGP-1, and NCI-H727 were treated with trametinib or SCH772984, alone and in combination with ribociclib, to assess cell proliferation, cell cycle distribution, and protein signaling using cell proliferation, flow cytometry, and Western blot assays, respectively.
resultsTrametinib and SCH772984, alone and in combination with ribociclib, significantly reduced NET cell viability and arrested NET cells at the G1 phase of the cell cycle in all three cell lines tested. In addition, trametinib also caused subG1 events and apoptotic PARP cleavage in QGP1 and NCI-H727 cells. A western blot analysis demonstrated the use of trametinib alone and trametinib in combination with ribociclib to decrease the expression of pERK, cMyc, Chk1, pChk2, pCDK1, CyclinD1, and c-myc in a time-dependent manner in NCI-H727 and QGP-1 cells.
conclusionsMEK and ERK inhibition causes antiproliferative effects in human NET cell lines in vitro. The combination of the MEK inhibitor trametinib (TMT212) with the CDK4/6 inhibitor ribociclib (LEE011) causes additive antiproliferative effects. Future preclinical and clinical studies of MEK inhibition in NETs should be performed.
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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.