Phase 1 clinical trialCombining a checkpoint inhibitor with an inhibitor of extracellular signal-regulated kinase (ERK) may result in synergistic antitumor activity. We evaluated MK-8353, an ERK1 and ERK2 inhibitor, plus pembrolizumab in a phase 1b study in patients with advanced solid tumors....
Approximately 10% of colorectal cancers harbor BRAF V600E mutations, which constitutively activate the MAPK signaling pathway. We sought to determine whether ERK inhibitor (GDC-0994)-containing regimens may be of clinical benefit to these patients based
Hutchmed (China) Limited (Hutchmed) has initiated a phase I study of HMPL-295, its investigative and highly selective oral inhibitor of ERK, which is a downstream component of the RAS-MAPK pathway signaling cascade. HMPL-295 has the potential to address intrinsic or acquired resistance from upst...
The novel ERK1/2 kinase inhibitor ulixertinib displayed an acceptable safety profile and had clinical activity in patients whose tumors had mutations in the MAPK cell-signaling pathway, according to data from aphase I clinical trialpublished inCancer Discovery, a journal of the American Association...
Antengene Announces First Patient Dosed in the Nivolumab Combination Portion of the Clinical Study Evaluating the ERK1/2 Inhibitor ATG-017 in Patients with Advanced Solid Tumors in the United States - ATG-017 isan oral, potent and selective small molecule ERK1/2 inhibitor. Antengene has exclusive...
Does BRAFV600Evs. KRASG13Damplification govern the distinct phenotypes of MEK1/2 inhibitor withdrawal? As with RAF, ectopic expression of mutant RAS can inhibit proliferation and induce senescence in human fibroblasts; indeed ectopic mutant RAS expression can promote these phenotypes even in tumour ...
Notably, Trametinib, an FDA-approved MEK inhibitor, enhances the efficacy of combination therapy with doxorubicin and IF. Overall, we have revealed the GSK3β-SIRT7 axis that must be fine-tuned in the face of the energetic and oncogenic stresses in malignancy....
And the AKT and EKT hyperphosphorylation contributes to erlotinib resistance might provide the indica- tion of combination with AKT/EKT inhibitor in clinical erlotinib therapy. Moreover, our finding might also suggest a mechanism of secondary drug tolerance in patients treated with erlo- tinib, ...
9. Infante, J. R. et al. A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas. Eur. J. Cancer 50, 2072–2081 (2014)....
In summary, the ERK inhibitor, ASTX029, has potent activity against MAPK-activated tumor models, including AML models, and is now being tested in a Phase 1/2 clinical trial in advanced solid tumors (NCT03520075). These data highlight its therapeutic potential for the treatment of AML in ...