PK-PD modeling of combination efficacy effect from administration of the MEK inhibitor GDC-0973 and PI3K inhibitor GDC-0941 in A2058 xenografts

12 views | Nov 20 2019

Choo EF et al. suggested that, based on minimal data, it is possible to predict the effects of various combinations preclinically and also assess the potential clinical efficacy of combinations using human pharmacokinetic inputs. [Read the Full Post]

U0126 attenuates ischemia/reperfusion-induced apoptosis and autophagy in myocardium through MEK/ERK/EGR-1 pathway

14 views | Nov 20 2019

Wang A et al. suggested that U0126 may protect against H/R injury by preventing H/R-induced myocardium apoptosis and autophagy via the MEK/ERK/EGR-1 pathway, and may be a potential therapeutic approach for attenuating myocardial I/R injury. [Read the Full Post]

Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity

19 views | Nov 05 2019

Bernstein A et al. found that Dual BRAF/MEK inhibitor therapy represents an exciting treatment option for patients with BRAF V600E primary brain tumors. In addition to greater efficacy than single-agent dabrafenib, this combination has the potential to mitigate cutaneous toxicity, one of the most common and concerning BRAF inhibitor-related adverse events. [Read the Full Post]

Real-world survival of patients with advanced BRAF V600 mutated melanoma treated with front-line BRAF/MEK inhibitors, anti-PD-1 antibodies, or nivolumab/ipilimumab

18 views | Nov 04 2019

Moser JC et al. found that patients with advanced BRAF mutant melanoma treated with front-line niv/ipi or aPD-1 had longer survival compared to those treated with front-line BRAF/MEKi. [Read the Full Post]

A phase I trial of the MEK inhibitor selumetinib (AZD6244) in pediatric patients with recurrent or refractory low-grade glioma: a Pediatric Brain Tumor Consortium (PBTC) study

38 views | Sep 01 2019

Banerjee A et al. indicated that selumetinib has promising antitumor activity in children with LGG. Rash and mucositis were the most common DLTs. [Read the Full Post]

Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas

47 views | Sep 01 2019

Dombi E et al. suggested that children with neurofibromatosis type 1 and inoperable plexiform neurofibromas benefited from long-term dose-adjusted treatment with selumetinib without having excess toxic effects. [Read the Full Post]

Inhibition of glioblastoma dispersal by the MEK inhibitor PD0325901

45 views | Aug 21 2019

Shannon S et al. showed that PD0325901 significantly increases aggregate cohesion, stiffness, and viscosity but only when tumor cells have access to high concentrations of fibronectin. Treatment also results in reorganization of actin from cortical into stress fibers, in both 2D and 3D culture. Moreover, drug treatment localized pFAK at sites of cell-substratum adhesion. Collectively, these changes resulted in increased strength of substrate attachment and decreased motility, a decrease in aggregate dispersal velocity, and in a marked decrease in growth rate of both 2D and 3D cultures. [Read the Full Post]

GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition

46 views | Jul 21 2019

Gilmartin AG et al. showed that GSK1120212 combines high potency, selectivity, and long circulating half-life, offering promise for successfully targeting the narrow therapeutic window anticipated for clinical MEK inhibitors. [Read the Full Post]

A DSTYK mutation activates ERK1/2 signaling to promote intraspinal dissemination in a case of solitary fibrous tumor/hemangiopericytoma

83 views | Jun 18 2019

Tang G et al. revealed the potential role of DSTYK mutation in the regulation of intraspinal metastasis of SFT/HPC, which might provide new biological insights into this rare disease. [Read the Full Post]

Trametinib Induces Neurofibroma Shrinkage and Enables Surgery

78 views | Jun 11 2019

Vaassen P et al. suggested that MEK inhibitors are likely to play a significant role in providing a cure for one of the most devastating manifestations of NF1. [Read the Full Post]