ArticleBritish journal of haematology2010
Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo.
Article in British journal of haematology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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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
65 citing papers in PubMed, 125 citations in OpenAlex.
- Pimasertib, a selective oral MEK1/2 inhibitor: absolute bioavailability, mass balance, elimination route, and metabolite profile in cancer patients.British journal of clinical pharmacology · 2016Trial
- A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Clinical, pharmacokinetic and pharmacodynamic data for the MEK1/2 inhibitor pimasertib in patients with advanced hematologic malignancies.Blood cancer journal · 2015Trial
- Phase I study of FOLFIRI plus pimasertib as second-line treatment for KRAS-mutated metastatic colorectal cancer.British journal of cancer · 2015Trial
- Machine-learning assisted subclassification of glioblastoma by developing an endoplasmic reticulum stress-related methylation signature.Frontiers in oncology · 2026Article
- Small molecule inhibitors for treating breast cancer: drug analysis based on the pathogenesis of breast cancer.Future medicinal chemistry · 2025Review
- Revealing the key role of cuproptosis in osteoporosis via the bioinformatic analysis and experimental validation of cuproptosis-related genes.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Three generations of mTOR kinase inhibitors in the activation of the apoptosis process in melanoma cells.Journal of cell communication and signaling · 2023Article
- Distinct longevity mechanisms across and within species and their association with aging.Cell · 2023Article
- Predicting anti-cancer drug combination responses with a temporal cell state network model.PLoS computational biology · 2023Article
- The role and regulation of Maf proteins in cancer.Biomarker research · 2023Review
- Site-Selective Amide Functionalization by Catalytic Azoline Engrafting.ACS catalysis · 2022Article
- Combination therapy targeting Erk1/2 and CDK4/6i in relapsed refractory multiple myeloma.Leukemia · 2022Article
- Immune landscape-based machine-learning-assisted subclassification, prognosis, and immunotherapy prediction for glioblastoma.Frontiers in immunology · 2022Article
- Review
- Obesity as a Possible Risk Factor for Progression from Monoclonal Gammopathy of Undetermined Significance Progression into Multiple Myeloma: Could Myeloma Be Prevented with Metformin Treatment?Advances in hematology · 2021Review
- Selective Oral MEK1/2 Inhibitor Pimasertib in Metastatic Melanoma: Antitumor Activity in a Phase I, Dose-Escalation Trial.Targeted oncology · 2021Article
- Selective Oral MEK1/2 Inhibitor Pimasertib: A Phase I Trial in Patients with Advanced Solid Tumors.Targeted oncology · 2021Article
- MicroRNA-126 promotes proliferation, migration, invasion and endothelial differentiation while inhibits apoptosis and osteogenic differentiation of bone marrow-derived mesenchymal stem cells.Cell cycle (Georgetown, Tex.) · 2020Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
This study investigated the cytotoxicity and mechanism of action of AS703026, a novel, selective, orally bioavailable MEK1/2 inhibitor, in human multiple myeloma (MM). AS703026 inhibited growth and survival of MM cells and cytokine-induced osteoclast differentiation more potently (9- to 10-fold) than AZD6244. Inhibition of proliferation induced by AS703026 was mediated by G0-G1 cell cycle arrest and was accompanied by reduction of MAF oncogene expression. AS703026 further induced apoptosis via caspase 3 and Poly ADP ribose polymerase (PARP) cleavage in MM cells, both in the presence or absence of bone marrow stromal cells (BMSCs). Importantly, AS703026 sensitized MM cells to a broad spectrum of conventional (dexamethasone, melphalan), novel or emerging (lenalidomide, perifosine, bortezomib, rapamycin) anti-MM therapies. Significant tumour growth reduction in AS703026- vs. vehicle-treated mice bearing H929 MM xenograft tumours correlated with downregulated pERK1/2, induced PARP cleavage, and decreased microvessels in vivo. Moreover, AS703026 (<200 nmol/l) was cytotoxic against the majority of tumour cells tested from patients with relapsed and refractory MM (84%), regardless of mutational status of RAS and BRAF genes. Importantly, BMSC-induced viability of MM patient cells was similarly blocked within the same dose range. Our results therefore support clinical evaluation of AS703026, alone or in combination with other anti-MM agents, to improve patient outcome.
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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.