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Blog of Signaling Pathways

The energy sensing LKB1-AMPKα1 pathway regulates IGF1 secretion and consequent activation of the IGF1R-PKB pathway in primary hepatocytes

140 views | Feb 06 2019

Chen L et al. demonstrated that the energy-sensing LKB1-AMPK pathway regulates IGF1 secretion in mouse primary hepatocytes, which in turn regulates activation of the IGF1R-PKB pathway. [Read the Full Post]

Inhibition of the NOTCH pathway using γ-secretase inhibitor RO4929097 has limited antitumor activity in established glial tumors

1100 views | Feb 05 2019

Dantas-Barbosa C et al. indicated that RO4929097-mediated effects were independent of NOTCH1 mutation status or expression levels, but associated with low IL-6 levels. In established glial tumor models, NOTCH inhibition had limited effects as a single agent, but enhanced efficacy when combined with DNA-interfering agents. These preclinical data need to be considered for further clinical development of NOTCH inhibitors in glial tumors. [Read the Full Post]

Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment

274 views | Feb 05 2019

Yee-Lin V et al. Nutlin-3, a small molecule inhibitor that specifically targets p53-Mdm2 interaction offers new therapeutic opportunities by enhancing cancer cell growth arrest and apoptosis through the restoration of the p53-mediated tumor suppression pathway while producing minimal cytotoxicity and side effects. [Read the Full Post]

Inhibition of Suicidal Erythrocyte Death by Volasertib

169 views | Feb 04 2019

Al Mamun Bhuyan A et al. volasertib is a novel inhibitor of erythrocyte cell membrane scrambling following energy depletion and hyperosmotic shock, effects contrasting the stimulation of K562 cell apoptosis. [Read the Full Post]

BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity

195 views | Feb 04 2019

Rudolph D et al. showed that with oral and i.v. routes of administration, the total weekly dose of BI 6727 is most relevant for efficacy, supporting the use of a variety of well-tolerated dosing schedules. [Read the Full Post]

Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer

281 views | Feb 03 2019

Valle J et al. showed that as compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer. [Read the Full Post]

Glutaminase inhibitor CB-839 synergizes with carfilzomib in resistant multiple myeloma cells

182 views | Feb 03 2019

Thompson RM et al. suggested that the acquisition of PI resistance involves adaptations in cellular bioenergetics, supporting the combination of CB-839 with Crflz for the treatment of refractory MM. [Read the Full Post]

Efficacy of the CDK inhibitor dinaciclib in vitro and in vivo in T-cell acute lymphoblastic leukemia

174 views | Feb 02 2019

Moharram SA et al. suggested that the CDK inhibitor dinaciclib is an active drug for T-ALL in the preclinical settings. [Read the Full Post]

Dinaciclib (SCH727965) inhibits the unfolded protein response through a CDK1- and 5-dependent mechanism

161 views | Feb 02 2019

Nguyen TK et al. highlight a link between specific components of the cell-cycle regulatory apparatus (e.g., CDK1/5) and the cytoprotective IRE1/XBP-1s/Grp78 arm of the UPR that may be exploited therapeutically in UPR-driven malignancies. [Read the Full Post]

Sulfoximines as ATR inhibitors: Analogs of VE-821

285 views | Feb 01 2019

Hendriks CMM et al. suggested that the sulfilimidoyl- and sulfoximidoyl-substituted analogs are efficient ATR inhibitors. [Read the Full Post]

The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia

191 views | Feb 01 2019

Brumatti G et al. demonstrated antileukemic efficacy and safety of the birinapant/emricasan combination in vivo suggest that induction of necroptosis warrants clinical investigation as a therapeutic opportunity in AML. [Read the Full Post]

The expression of endothelin-1 in chronic lymphocytic leukemia is controlled by epigenetic mechanisms and extracellular stimuli

134 views | Jan 31 2019

Martinelli S et al. demonstrated the fundamental role of NF-kB signalling pathway in promoting and maintaining ET-1 expression in CLL cells, both in basal conditions and after CD40 activation. [Read the Full Post]

Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity

0 views | Jan 30 2019

Godoy LD et al. provided the first step in identifying multiple bioactive compound HDAC inhibitors. [Read the Full Post]

Molecular regulation of apoptotic machinery and lipid metabolism by mTORC1/mTORC2 dual inhibitors in preclinical models of HER2+/PIK3CAmut breast cancer

292 views | Jan 30 2019

Qian J et al. found that the basal levels of carnitine palmitoyltransferase 1A and lipid catabolism were elevated in HER2+/PIK3CAmut breast cells and were inhibited upon mTOR-KI treatment. [Read the Full Post]

MDM2 is implicated in high-glucose-induced podocyte mitotic catastrophe via Notch1 signalling

165 views | Jan 29 2019

Tang H, et al. found that high glucose up-regulates MDM2 expression and leads to podocyte MC. Notch1 signalling is an essential downstream pathway of MDM2 in mediating HG-induced MC in podocytes. [Read the Full Post]

Expression and function of MutT homolog 1 in distinct subtypes of breast cancer

144 views | Jan 29 2019

Treatment with the MTH1 inhibitor appears to be safe; however, further studies are required prior to the clinical use of MTH1 inhibitors. [Read the Full Post]

Inhibition of γ-secretase activity synergistically enhances tumour necrosis factor-related apoptosis-inducing ligand induced apoptosis in T-cell acute lymphoblastic leukemia cells via upregulation of death receptor 5

175 views | Jan 28 2019

Greene LM et al. found that DAPT/TRAIL apoptotic synergy was dependent on the extrinsic apoptotic pathway and was associated with a decrease in BH3 interacting-domain death agonist and x-linked inhibitor of apoptosis. In conclusion, γ-secretase inhibition represents a potential therapeutic strategy to overcome TRAIL resistance for the treatment of T-ALL. [Read the Full Post]

Drp1 mediates compression-induced programmed necrosis of rat nucleus pulposus cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF

171 views | Jan 28 2019

Lin H et al. indicated that Drp1 mediates compression-induced programmed necrosis of NP cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF. [Read the Full Post]

Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

0 views | Jan 27 2019

Du J et al. suggested SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway. [Read the Full Post]

v-Src Oncogene Induces Trop2 Proteolytic Activation via Cyclin D1

149 views | Jan 27 2019

Ju X et al. found that Cyclin D1 serves as a transducer of v-Src-mediated induction of Trop2 ICD by enhancing abundance of the Trop2 proteolytic activation complex. [Read the Full Post]