Blog of Signaling Pathways

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

489 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

838 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

537 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

478 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

655 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

571 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

639 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

481 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

469 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

404 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]

Role of connexin 43 in cadmium-induced proliferation of human prostate epithelial cells

454 views | Jan 26 2019

Liu Q et al. found that Cx43 might be a target for prostatic diseases associated with Cd exposure. [Read the Full Post]

Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms

485 views | Jan 26 2019

Diamond EL et al. highlighted the importance of comprehensive genomic analysis of these disorders. [Read the Full Post]

27 T ultra-high static magnetic field changes orientation and morphology of mitotic spindles in human cells

739 views | Jan 25 2019

Zhang L et al. not only found that ultra-high magnetic field can change the orientation and morphology of mitotic spindles, but also provided a tool to probe the role of spindle orientation and perturbation in developmental and cancer biology. [Read the Full Post]

Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin

1144 views | Jan 25 2019

Hiramoto K et al. suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma. [Read the Full Post]

Synergistic antitumor effect of NVP-BEZ235 and CAPE on MDA-MB-231 breast cancer cells

704 views | Jan 24 2019

Torki S et al. suggested that tumor metastasis and progression in TNBC cells can be effectively reduced through the concurrent use of NVP-BEZ235 and CAPE. This could be of particular interest in assessing the effects of this therapy in the reduction of tumor metastasis and progression in other tumor types. [Read the Full Post]

Phase Ib dose-finding study of abiraterone acetate plus buparlisib (BKM120) or dactolisib (BEZ235) in patients with castration-resistant prostate cancer

716 views | Jan 24 2019

Massard C et al. indicated that based on the assessment of available pharmacokinetics, safety, and efficacy data, no further study is planned for either buparlisib or dactolisib in combination with AA in CRPC. [Read the Full Post]

A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening

992 views | Jan 23 2019

Yan HHN et al. indicated this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy. [Read the Full Post]

Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor-Naïve Advanced Pancreatic Neuroendocrine Tumors

2474 views | Jan 23 2019

Salazar R et al. showed thta BEZ235 treatment in mTOR inhibitor-naïve patients with advanced pNET did not demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile. [Read the Full Post]