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Blog of Signaling Pathways

An Oncogenic ALK Fusion and an RRAS Mutation in KRAS Mutation-Negative Pancreatic Ductal Adenocarcinoma

0 views | Feb 09 2019

Shimada Y et al. found that rare oncogenic aberrations, such as the ALK fusion and RRAS mutation, may drive pancreatic carcinogenesis independent of the KRAS mutation. [Read the Full Post]

PBX3 is essential for leukemia stem cell maintenance in MLL-rearranged leukemia

109 views | Feb 08 2019

Guo H et al. found that PBX3 is epigenetically aberrant in the LSCs of MLL-r AML and is essential for leukemia development. Significantly, the differential expression of PBX3 in normal and malignant hematopoietic cells suggests PBX3 as a potential prognostic marker and therapeutic target for MLL-r leukemia. [Read the Full Post]

MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values

93 views | Feb 08 2019

Lee GD et al. found that the prognosis of patients with METex14 skipping was similar to that of patients with major driver mutations. siRNA targeting the junction of METex14 skipping could inhibit MET-driven signaling pathways in cells with METex14 skipping. [Read the Full Post]

Inhibition of oxidative phosphorylation suppresses the development of osimertinib resistance in a preclinical model of EGFR-driven lung adenocarcinoma

199 views | Feb 07 2019

Martin MJ et al. supported a model in which the combination of osimertinib and OxPhos inhibitors can delay or prevent resistance in osimertinib-naïve tumour cells, and represents a novel strategy that warrants further pre-clinical investigation. [Read the Full Post]

Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors

251 views | Feb 07 2019

CXCL12 competition binding studies were proven to be highly valuable as an initial screening assay and indicative for the pharmacological and functional profile of competitive CXCR4 antagonists, which will help the design of new potent CXCR4 inhibitors. [Read the Full Post]

Fatty acid translocase promoted hepatitis B virus replication by upregulating the levels of hepatic cytosolic calcium

212 views | Feb 06 2019

Huang J et al. identified a novel link between CD36 and HBV replication, which is associated with cytosolic calcium and the Src kinase pathway. [Read the Full Post]

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

100 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

754 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

187 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

108 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

133 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

210 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

127 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

114 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

108 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

209 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

126 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

88 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

205 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]