Blog of Signaling Pathways

Proteomic Analysis of an Induced Pluripotent Stem Cell Model Reveals Strategies to Treat Juvenile Myelomonocytic Leukemia

434 views | Feb 05 2020

Pearson S et al. demonstrated these small molecular inhibitors, JQ1 and CBL0137, preferentially extinguish primitive hematopoietic cells from sporadic JMML patients as opposed to cells from healthy individuals. [Read the Full Post]

CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant

421 views | Feb 04 2020

Sakamoto H et al. supported the potential for clinical evaluation of CH5424802 for the treatment of patients with ALK-driven tumors. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

0 views | Feb 04 2020

Svoboda LK et al. demonstrated that the SSP is highly active in Ewing sarcoma and that its oncogenic activation is maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]

Protein tyrosine kinase 2: a novel therapeutic target to overcome acquired EGFR-TKI resistance in non-small cell lung cancer

538 views | Feb 03 2020

Tong X et al. suggested that this combination therapy may be a viable option to overcome EGFR-TKI resistance in NSCLC. [Read the Full Post]

PD98059 protects the brain against mitochondrial-mediated apoptosis and autophagy in a cardiac arrest rat model

364 views | Feb 03 2020

Zheng JH et al. showed that PD98059 decreased the openings of MPTP, CytC release, caspase3 activation, apoptotic indices, LC3-II, Beclin-1and increased P62. PD98059 also inhibited mitochondria-dependent apoptosis and the activity of autophagy in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. The generation of phosphorylated Drp1-616 was down-regulated accompanied by a decrease of TUNEL-positive cells and LC3 in dual immunostaining after PD98059 inhibited activation of ERK signaling pathway in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. [Read the Full Post]

Treatment outcome and clinical characteristics of HER2 mutated advanced non-small cell lung cancer patients in China

543 views | Feb 01 2020

Fei Xu et al. found that HER2 mutated lung cancer patients were younger, mostly females, never or light smokers, with histologically diagnosed adenocarcinomas. Compared with afatinib, chemotherapy might bring more benefit to HER2 mutated advanced lung cancer patients, especially the most common type of HER2 exon 20 insertions, A775_G776insYVMA subtype. [Read the Full Post]

Determination of Somatic Mutations and Tumor Mutation Burden in Plasma by CAPP-Seq during Afatinib Treatment in NSCLC Patients Resistance to Osimertinib

558 views | Feb 01 2020

Ishii H et al. demonstrated that detection of mutant allele frequency and TMB of ctDNA by CAPP-Seq could help determine the effectiveness of and resistance to afatinib. [Read the Full Post]

EZH2 targeting reduces medulloblastoma growth through epigenetic reactivation of the BAI1/p53 tumor suppressor pathway

530 views | Jan 31 2020

Zhang H et al. demonstrated that reactivation of BAI1 expression underlies EPZ-6438 antitumorigenic action, and provided preclinical proof-of-principle evidence for targeting EZH2 in patients with MB. [Read the Full Post]

Analyses of FGFR3 and PIK3CA mutations in neuroblastomas and the effects of the corresponding inhibitors on neuroblastoma cell lines

270 views | Jan 31 2020

Kostopoulou ON et al. demonstrated that FGFR3 and PIK3CA mutations are uncommon in patients with NB. [Read the Full Post]

The small molecule AZD6244 inhibits dengue virus replication in vitro and protects against lethal challenge in a mouse model

336 views | Jan 30 2020

de Oliveira LC et al. demonstrated the potential of AZD6244 as a new therapeutic agent to treat DENV infection and possibly other flavivirus diseases. [Read the Full Post]

MTA1 promotes tumorigenesis and development of esophageal squamous cell carcinoma via activating the MEK/ERK/p90RSK signaling pathway

349 views | Jan 30 2020

Nan P et al. found that MTA1 plays a pivotal oncogenic role in ESCC tumorigenesis and development through activating the MEK/ERK/p90RSK pathway. [Read the Full Post]

Multi-Platform Omics Analysis for Identification of Molecular Characteristics and Therapeutic Targets of Uveal Melanoma

157 views | Jan 29 2020

Kim YJ et al. identified high MYC activity in UVM, and suggested G2/M checkpoint inhibitors as effective therapeutic targets for UVM. [Read the Full Post]

Combined tazemetostat and MAPKi enhances differentiation of papillary thyroid cancer cells harbouring BRAFV600E by synergistically decreasing global trimethylation of H3K27

350 views | Jan 29 2020

Fu H et al. found that tazemetostat combined with MAPKi enhances differentiation of PTC cells harbouring BRAFV600E through synergistically decreasing global trimethylation of H3K27, representing a novel differentiation strategy. [Read the Full Post]

Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001

402 views | Jan 28 2020

Shaw AT et al. showed the clinically meaningful benefit and safety of crizotinib in this molecular subgroup. [Read the Full Post]

Daratumumab prevents programmed death ligand-1 expression on antigen-presenting cells in de novo multiple myeloma

424 views | Jan 28 2020

Stocker N et al. suggested new mechanisms of action of Dara through depletion of pDC and prevention of PD-L1 upregulation expression on APC. Our finding provides new evidences for development of therapeutic strategies targeting both CD38 and PD-L1/PD-1 pathway in patients with MM. [Read the Full Post]

Discovery and development of Seliciclib. How systems biology approaches can lead to better drug performance

286 views | Jan 27 2020

Khalil HS et al. argue that optimisation of the therapeutic effects of kinase inhibitors such as Seliciclib could be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division. [Read the Full Post]

Tumor-Directed Therapeutic Targets in Cushing Disease

306 views | Jan 27 2020

Theodoropoulou M et al. indicated that for many patients with CD, effective tumor-targeted pharmacological therapy is still lacking. Coordinated efforts are pivotal in establishing efficacy and safety of novel therapeutics in this rare but devastating disease. [Read the Full Post]

Protective effect of roscovitine against rotenone-induced parkinsonism

288 views | Jan 26 2020

Chen Y et al. indicated that mouse models of Parkinson's disease were established by oral rotenone administration and reproduced some of the features of dopaminergic neuronal degeneration. Roscovitine protects against rotenone-induced parkinsonism. [Read the Full Post]

Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC)

533 views | Jan 25 2020

Yang PW et al. demonstrated that both cabozantinib and R428 inhibit ESCC growth in cell and xenograft models. The results reveal the great potential of using cabozantinib for targeted therapy of ESCC. [Read the Full Post]

Cost-effectiveness of midostaurin in the treatment of newly diagnosed FLT3-mutated acute myeloid leukemia in France

496 views | Jan 25 2020

Tremblay G et al. indicated that MIDO represents a clinically significant advancement in the management of newly diagnosed FLT3-mutated AML. In this analysis, MIDO add-on therapy showed gains in LYs and QALYs versus SOC alone and was found to be a cost-effective option at a €100,000 per QALY threshold for end-of-life treatment. [Read the Full Post]