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Blog of Signaling Pathways

Synthetic Lethality Exploitation by an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132, Plus PARP Inhibitors in BRCA1/2-wild-type Triple-Negative Breast Cancer

1313 views | Oct 20 2017

Cardillo TM et al. demonstrated the added benefit of combining Topo I inhibition mediated by IMMU-132 with synthetic lethality provided by PARPi in TNBC, regardless of BRCA1/2 status, thus supporting the rationale for such a combination clinically. [Read the Full Post]

Nuclear Export of Ubiquitinated Proteins Determines the Sensitivity of Colorectal Cancer to Proteasome Inhibitor

665 views | Oct 20 2017

Wu T et al. indicated that nuclear p53 is a major mediator in the synergistic antitumor effect of bortezomib and KPT330, and provides a rationale for the use of proteasome inhibitor together with nuclear export blocker in the treatment of colorectal cancer. It is conceivable that targeting nuclear exportation may serve as a novel strategy to overcome resistance and raise chemotherapeutic efficacy, especially for the drugs that activate the p53 system. [Read the Full Post]

Crosstalk between the IGF-1R/AKT/mTORC1 pathway and the tumor suppressors p53 and p27 determines cisplatin sensitivity and limits the effectiveness of an IGF-1R pathway inhibitor

606 views | Oct 19 2017

Davaadelger B, et al. demonstrated 1) p53 expression determines the effect of IGF-1R inhibition on cancer cell CP response, and 2) crosstalk between the IGF-1R/AKT/mTORC1 pathway and p53 and p27 can reduce cancer cell responsiveness to chemotherapy and may ultimately limit the effectiveness of IGF-1R pathway inhibitors in the clinic. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 views | Oct 19 2017

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 views | Oct 18 2017

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

2753 views | Oct 17 2017

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [Read the Full Post]

Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis

1648 views | Oct 16 2017

Zhang F et al. provided evidence that the canonical hedgehog pathway controlled HSC-mediated liver angiogenesis. Selective inhibition of HSC hedgehog signalling could be a promising therapeutic approach for hepatic fibrosis. [Read the Full Post]

Resistance Mechanism against Trastuzumab in HER2-Positive Cancer Cells and Its Negation by Src Inhibition

1239 views | Oct 16 2017

Jin MH et al. suggested that Src inhibition may be an effective measure to overcome trastuzumab resistance in HER2-positive cancer. [Read the Full Post]

Improved fluorescence assays to measure the defects associated with F508del-CFTR allow identification of new active compounds

0 views | Oct 15 2017

Langron E et al. showed that most known potentiators have a negative influence on F508del-CFTR biogenesis/stability, which means membrane exposure needs to be monitored early during the development of drugs targeting CFTR. The combined use of the two fluorescence assays described here provides a useful tool for the identification of improved potentiators and correctors. The assays could also prove useful for basic scientific investigations on F508del-CFTR, and other CF-causing mutations. [Read the Full Post]

Mechanistic Approaches to Improve Correction of the Most Common Disease-Causing Mutation in Cystic Fibrosis

752 views | Oct 14 2017

Bali V et al. emphasized that stabilization of ΔF508 CFTR band B in the ER might improve its functional rescue by Orkambi. [Read the Full Post]

The Tumor-Associated Glycosyltransferase ST6Gal-I Regulates Stem Cell Transcription Factors and Confers a Cancer Stem Cell Phenotype

963 views | Oct 14 2017

Schultz MJ et al. found that ST6Gal-I induced expression of the key tumor-promoting transcription factors, Sox9 and Slug [Read the Full Post]

Protective effect of necrostatin-1 on myocardial tissue in rats with acute myocardial infarction

0 views | Oct 13 2017

Liu YR et al. found that necrostatin-1 can inhibit myocardial tissue apoptosis and necrosis in acute myocardial infarct rats and has a protective effect on myocardial tissue. [Read the Full Post]

Antagonizing Integrin β3 Increases Immunosuppression in Cancer

763 views | Oct 13 2017

Su X et al. suggest that effects of integrin β3 therapies on immune cells should be considered to improve outcomes. [Read the Full Post]

Expression and clinical significance of Wee1 in colorectal cancer

0 views | Oct 12 2017

Egeland EV et al. indicated that other tumor types might be better suited for further development of Wee1 inhibitors. [Read the Full Post]

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma

0 views | Oct 12 2017

Saha SK et al. provided a systematic and broadly applicable approach to define targets of kinase inhibitors underlying drug responsiveness. [Read the Full Post]

SP600125 enhances the anti-apoptotic capacity and migration of bone marrow mesenchymal stem cells treated with tumor necrosis factor-α

1030 views | Oct 11 2017

Wei B et al. suggested that SP600125 is of potential use in promoting the regeneration of bone and cartilage in OA and RA. [Read the Full Post]

miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A

0 views | Oct 11 2017

Chang X et al. reveal that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. [Read the Full Post]

Effects of bavachin and its regulation of melanin synthesis in A375 cells

0 views | Oct 10 2017

Wang JH, et al. found that bavachin inhibited the synthesis of melanin on A375 cells by inhibiting the protein and mRNA expression of TYR, TRP-1, TRP-2, ERK1, ERK2 andJNK2. [Read the Full Post]

Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer

754 views | Oct 10 2017

Ju HQ et al. suggested that Nampt inhibition may override gemcitabine resistance by decreasing the NAD level and suppressing glycolytic activity, warranting further clinical investigation for pancreatic cancer treatment. [Read the Full Post]

Nucleoside Inhibitors of Zika Virus

0 views | Oct 09 2017

Eyer L, et al. suggested that these compounds might represent promising lead candidates for further development of specific antivirals against ZIKV. [Read the Full Post]