A Phase Ib Study to Evaluate the MEK Inhibitor Cobimetinib in Combination with the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors

19 views | Dec 19 2020

Colin Weekes et al. thought that overlapping AEs and cumulative toxicity could not be adequately managed on either dosing schedule, restricting the ability to further develop this combination. [Read the Full Post]

Inhibition of the ERK/RSK kinase cascade limits Chlamydia trachomatis infection

39 views | Oct 04 2020

Yaohua Xue et al. demonstrated not only that the ERK/RSK pathway played a critical role in Chlamydia infection, but also that these kinases had potential as targets for host-directed therapy against Chlamydia trachomatis. [Read the Full Post]

NRAS Status Determines Sensitivity to SHP2 Inhibitor Combination Therapies Targeting the RAS-MAPK Pathway in Neuroblastoma

37 views | Oct 04 2020

Ivette Valencia-Sama et al. suggested that conventional therapy-resistant, relapsed neuroblastoma might be effectively treated via combined inhibition of SHP2 and MEK or ERK of the RAS-MAPK pathway. [Read the Full Post]

Proteasome Inhibitor PS-341 Effectively Blocks Infection by the Severe Fever with Thrombocytopenia Syndrome Virus

102 views | Aug 07 2020

Sihua Liu et al. indicated that targeting of cellular interferon pathways and apoptosis during acute infection might serve as the bases of future therapeutics for the treatment of SFTSV infections. [Read the Full Post]

Sequential Bortezomib and Temozolomide Treatment Promotes Immunological Responses in Glioblastoma Patients With Positive Clinical Outcomes: A Phase 1B Study

141 views | Jun 25 2020

Mohummad A Rahman et al. found that Sequential BTZ + TMZ treatment was safe and promotes Th1-driven immunological responsed in selected patients with improved clinical outcomes ( (NCT03643549)). [Read the Full Post]

Loss of HAT1 Expression Confers BRAFV600E Inhibitor Resistance to Melanoma Cells by Activating MAPK Signaling via IGF1R

90 views | Jun 07 2020

Suresh Bugide et al. showed that the loss of HAT1 expression confered acquired BRAFi resistance by activating the MAPK signaling pathway via IGF1R. [Read the Full Post]

A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors

118 views | Mar 17 2020

Varga A et al. indicated that GDC-0994 had an acceptable safety profile and pharmacodynamic effects were observed by FDG-PET and in serial tumor biopsies. Single-agent activity was observed in 2 patients with BRAF-mutant colorectal cancer. [Read the Full Post]

Automobile exhaust-derived PM2.5 induces blood-testis barrier damage through ROS-MAPK-Nrf2 pathway in sertoli cells of rats

0 views | Jan 19 2020

Liu B et al. indicated that PM2.5 derived from automobile exhaust causes oxidative stress, which in turn causes cellular apoptosis of SCs and damage of the blood-testis barrier, resulting male spermatogenesis dysfunction, in which ROS-MAPK-Nrf-2 pathways may play a key role. [Read the Full Post]

In Silico Screening Reveals Histone Deacetylase 7 and ERK1/2 as Potential Targets for Artemisinin Dimer and Artemisinin Dimer Hemisuccinate

141 views | Dec 11 2019

Ishola AA et al. suggested that artemisinin dimer and artemisinin dimer hemisuccinate could be promising anticancer drug agents, with better therapeutic efficacy than ulixertinib and apicidin in the treatment of cancer via inhibition of HDAC7, ERK1 and ERK2. [Read the Full Post]

LKB1 deficiency renders non-small-cell lung cancer cells sensitive to ERK inhibitors.: ERK inhibitors in LKB1 mutated NSCLC

156 views | Dec 11 2019

Caiola E et al. showed that ERK inhibitors are effective in LKB1 and LKB1/KRAS mutated tumors, thus offering a therapeutic strategy for this prognostically unfavorable subgroup of patients. Since ERK inhibitors are already in clinical development, our findings could be easily translatable to the clinic. Importantly, the lack of effect in cells expressing wild-type LKB1, predicts that treatment of LKB1 mutated tumors with ERK inhibitors should have a favorable toxicity profile. [Read the Full Post]