MEK INHIBITION
Therapeutic efficacy of combined BRAF and MEK inhibition in metastatic melanoma: a comprehensive network meta-analysis of randomized controlled trials
... sorafenib) inhibition, as compared with chemotherapy, have provided considerable clinical benefits including progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) in patients ...
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Therapeutic efficacy and safety of combined <em>BRAF</em> and MEK inhibition in patients with malignant melanoma: a meta-analysis
... and MEK inhibition was associated with a significant improvement in overall response, progression-free survival, and overall survival, but increased the incidence of adverse events among the patients with ...
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Sustained MEK inhibition abrogates myeloproliferative disease in Nf1 mutant mice
... counts, enhanced erythropoiesis, and markedly smaller spleens by the end of the trial (Figure 1, A–D). Whereas most Nf1 mutant mice survived (Figure 1E), mice assigned to the vehicle group were disheveled and losing ...
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MEK inhibition induces apoptosis in osteosarcoma cells with constitutive ERK1/2 phosphorylation
... three MEK inhibitors in a 3D culture system validated efficacy in inhibition of osteosarcoma ...MEK1/2 inhibition represents a candidate treatment strategy for osteosarcomas displaying high ...
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Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells
... is not feasible due to potential side effects (27), additional strategies are required. The ratio of ERK1/2 to p38 MAPK activity has been shown to be a determinant of the proliferative or dormant state of human head and ...
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MEK inhibition induced downregulation of MRP1 and MRP3 expression in experimental hepatocellular carcinoma
... the inhibition of MAPK pathway and its role in regulating HCC cell growth as well as ABC proteins MRP1 and MRP3 ...different MEK inhibitors (U0126 and AZD6244) were used to treat HCC cells to identify their ...
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Synchronous BRAFV600E and MEK inhibition leads to superior control of murine melanoma by limiting MEK inhibitor induced skin toxicity
... exact mechanism that mediates the MEKi-associated skin toxicity remains unclear. Signaling proteins downstream of pERK might be involved in the skin toxicity mechanism as well. Although speculative, concomitant BRAFi may ...
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MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors
... PD0325901 inhibits MEK and moderately reduces MPNST cell survival in vitro. To identify molecular similarities between mouse and human NF1 tumors, we performed cross-species transcriptome analysis of human ...
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Treatment of B RAF mutant human tumor cells with a MEK inhibitor requires Bim and is enhanced by a BH3 mimetic
... the MEK/ERK signaling pathway and ultimately tumor cell growth and ...survival. MEK inhibition in these cells results in cell cycle arrest and cytosta- ...that MEK inhibition also ...
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Phosphorylation of Beta 3 adrenergic receptor at serine 247 by ERK MAP kinase drives lipolysis in obese adipocytes
... vivo MEK inhibition for upstream effectors (Figure ...by MEK inhibitor treatment (Figure 6B), suggesting that ERK phosphory- lates b 3AR speci fi cally at residue serine ...
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In pursuit of synergy: An investigation of the PI3K/mTOR/MEK co-targeted inhibition strategy in NSCLC
... and MEK inhibitors in the clinic may involve a failure to induce apoptosis via BCL-2 family proteins ...and MEK inhibitors in ...and MEK inhibition, implying a role for targeting specific ...
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A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors
... AKT inhibition and sensitivity to MEK inhibition in cell line panels inde- pendent of KRAS mutation status, that the signature is downregulated by MEK inhibition, and that the signature ...
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Inhibition of the PI3K but not the MEK/ERK pathway sensitizes human glioma cells to alkylating drugs
... targeted MEK with two specific inhib- itors, U0126 and PD98059, ...for MEK inhibition ...Conversely, MEK inhibi- tion even tended to desensitize cells for TMZ treat- ment and this effect was ...
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Mirk/Dyrk1B mediates G0/G1 to S phase cell cycle progression and cell survival involving MAPK/ERK signaling in human cancer cells
... [2]. Inhibition of MAPK/ERK activity by removal of serum mitogen [20] or by addition of the MEK inhibitor increased endogenous Mirk/Dyrk1B protein levels and its promoter construct [2], suggesting ...
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Receptor tyrosine kinase-dependent PI3K activation is an escape mechanism to vertical suppression of the EGFR/RAS/MAPK pathway in KRAS-mutated human colorectal cancer cell lines
... to MEK-inhibition ...ing MEK inhibition is correlated to RTK activity, paving the way to the use of RTK inhibitors in KRAS mutated CRC ...and MEK over- comes both acquired and primary ...
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MEK-Specific Inhibitor U0126 Blocks Spread of Borna Disease Virus in Cultured Cells
... or inhibition of virus entry into the ...the MEK inhib- ...upon inhibition of the signaling cascade. Inhibition was no longer successful if U0126 was added 4 h ...that inhibition of the ...
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Titration of signalling output: insights into clinical combinations of MEK and AKT inhibitors.
... of MEK and AKT ...of MEK inhibition as it downstream of ...AKT inhibition as allosteric and ATP competitive drugs used to inhibit AKT caused diamet- rically opposite effects on phosphorylation ...
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mTOR and MEK1/2 inhibition differentially modulate tumor growth and the immune microenvironment in syngeneic models of oral cavity cancer
... that MEK inhibition inhibits but mTOR inhibition relatively preserves anti-tumor T-cell responses both via tetramer- based flow cytometry in MOC1 tumor tissue and in an in vitro T-cell proliferation ...
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Mutant HRAS as novel target for MEK and mTOR inhibitors
... whether MEK inhibitors could be of relevance for treatment of HRAS mutated ...for MEK inhibition than HRAS wild-type cells such as CAL12T, HCC44, HCC827 and HCC78 (Figure 1C,1D, Supplementary Figure ...
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New Cancer Immunotherapy Agents in Development: a report from an associated program of the 31stAnnual Meeting of the Society for Immunotherapy of Cancer, 2016
... that MEK inhibition has positive immunomodulatory effects including intratu- moral T cell accumulation and upregulation of MHC class I, potentially promoting antigen presentation and tumor ...of MEK ...
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