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Blog of Signaling Pathways

RAF Dimer Inhibition Enhances the Antitumor Activity of MEK Inhibitors in K-RAS Mutant Tumors

21 views | Jun 20 2020

Xi Yuan et al. supported a vertical inhibition strategy in which RAF dimer and MEKi are combined to target K-RAS-mutated cancers, and have led to a Phase 1b/2 combination therapy study of lifirafenib and mirdametinib in solid tumor patients with K-RAS mutations and other MAPK pathway aberrations. [Read the Full Post]

Targeting the Ubiquitin-Proteasome Pathway to Overcome Anti-Cancer Drug Resistance

15 views | Jun 20 2020

Silpa Narayanan et al. discussed various PIs and their underlying mechanisms in surmounting anti-tumor drug resistance when used in combination with conventional chemotherapeutic agents. [Read the Full Post]

Inhibition of Aurora Kinase A by Alisertib Reduces Cell Proliferation and Induces Apoptosis and Autophagy in HuH-6 Human Hepatoblastoma Cells

15 views | Jun 19 2020

Jingyi Tan et al. suggested that AURKA may be a novel therapeutic target and ALS a potential therapeutic drug for the treatment of HB. [Read the Full Post]

Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases

24 views | Jun 19 2020

James Chih-Hsin Yang et al. found that Afatinib has clinical activity in NSCLC against major uncommon and compound EGFR mutatios. It also has broad activity against other uncommon EGFR mutations and some exon 20 insertions. The data support the use of afatinib in these settings. [Read the Full Post]

DAPT Score and the Impact of Ticagrelor Monotherapy During the Second Year After PCI

26 views | Jun 18 2020

Ply Chichareon et al. found that the DAPT score can stratify ischemic but not bleeding risk in a contemporary PCI population during the second year. [Read the Full Post]

Staurosporine and NEM Mainly Impair WNK-SPAK/OSR1 Mediated Phosphorylation of KCC2 and NKCC1

44 views | Jun 18 2020

Jinwei Zhang et al. identified phospho-sites that are responsive to staurosporine or NEM application. [Read the Full Post]

Prediction of Therapeutic Outcome and Survival in a Transgenic Mouse Model of Pancreatic Ductal Adenocarcinoma Treated With Dendritic Cell Vaccination or CDK Inhibitor Using MRI Texture: A Feasibility Study

10 views | Jun 17 2020

Aydin Eresen et al. demonstrated that MRI texture features had great potential to generate diagnosis and prognosis models for monitoring early treatment response following dinaciclib drug or DC vaccine treatment and also predicting histopathological tumor markers and long-term clinical outcomes. [Read the Full Post]

Revealing the Selective Mechanisms of Inhibitors to PARP-1 and PARP-2 via Multiple Computational Methods

19 views | Jun 17 2020

Hongye Hu et al. provided new insights about how inhibitors specifically bound to PARP-1 over PARP-2, which might help facilitate the design of highly selective PARP-1 inhibitors in the future. [Read the Full Post]

Xiaochaihu Decorction Relieves Liver Fibrosis Caused by Schistosoma Japonicum Infection via the HSP47/TGF-β Pathway

13 views | Jun 16 2020

Yuzheng Huang et al. demonstrated that the hepatic protective effects of Xiaochaihu decoction were mediated by HSP47/TGF-β axis. [Read the Full Post]

Cooperativity Between Orthosteric Inhibitors and Allosteric Inhibitor 8-Anilino-1-Naphthalene Sulfonic Acid (ANS) in Cyclin-Dependent Kinase 2

15 views | Jun 16 2020

Erik B Faber et al. detailed the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increased the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. [Read the Full Post]

STMN1 Upregulation Mediates Hepatocellular Carcinoma and Hepatic Stellate Cell Crosstalk to Aggravate Cancer by Triggering the MET Pathway

20 views | Jun 15 2020

Rui Zhang et al. suggested that STMN1 may be used as a potential marker to identify patients who may benefit from MET inhibitor treatment. [Read the Full Post]

Mechanism and Current Progress of Poly ADP-ribose Polymerase (PARP) Inhibitors in the Treatment of Ovarian Cancer

0 views | Jun 15 2020

Feiyue Zheng et al. highlighted the current research progress on PARP inhibitor resistance, which has become a challenge in clinics. [Read the Full Post]

LGR5 Controls Extracellular Matrix Production by Stem Cells in the Developing Intestine

32 views | Jun 14 2020

Valeria Fernandez Vallone et al. provided that Lgr5 antagonizes the Rspondin 2-Wnt-mediated response in ISCs in organoids, revealing a sophisticated regulatory process for Wnt signaling in ISCs. [Read the Full Post]

Promotion of Liver Regeneration and Anti‑fibrotic Effects of the TGF‑β Receptor Kinase Inhibitor Galunisertib in CCl4‑treated Mice

10 views | Jun 14 2020

Atsutaka Masuda et al. suggested that galunisertib might be an effective treatment for liver cirrhosis. [Read the Full Post]

HO-1 Downregulation Favors BRAF V600 Melanoma Cell Death Induced by Vemurafenib/PLX4032 and Increases NK Recognition

37 views | Jun 13 2020

Anna L Furfaro et al. indicated that HO-1 downregulation can both improve the efficacy of Vemurafenib on melanoma cells and favor melanoma susceptibility to NK cell-mediated recognition and killing. [Read the Full Post]

Calcium Signaling Mediated by Aminergic GPCRs Is Impaired by the PI3K Inhibitor LY294002 and Its Analog LY303511 in a PI3K-independent Manner

17 views | Jun 13 2020

Polina D Kotova et al. found that LY303511 and LY294002 should be used cautiously in studies of PI3K as a factor of GPCR signaling. [Read the Full Post]

Network Indirect Comparison of 3 BRAF + MEK Inhibitors for the Treatment of Advanced BRAF Mutated Melanoma

22 views | Jun 12 2020

F Consoli et al. suggested a similar efficacy and a slightly different safety profile, related to specific molecular properties of the three different BRAF and MEK inhibitors currently approved in the management of advanced MM. [Read the Full Post]

AXL Controls Directed Migration of Mesenchymal Triple-Negative Breast Cancer Cells

16 views | Jun 11 2020

Olivier Zajac et al. demonstrated that AXL controls directed cell migration most likely by regulating cell polarity. [Read the Full Post]

Combined Therapy of AXL and HDAC Inhibition Reverses Mesenchymal Transition in Diffuse Intrinsic Pontine Glioma

17 views | Jun 11 2020

Michaël H Meel et al. found that combined inhibition of AXL and HDACs in DIPG cells results in a synergistic antitumor effect by reversing their mesenchymal, stem cell-like, therapy-resistant phenotype. [Read the Full Post]

The Effects of NLRP3 Inflammasome Inhibition by MCC950 on LPS-induced Pancreatic Adenocarcinoma Inflammation

11 views | Jun 10 2020

Alan Cheuk Keong Yaw et al. showed there was a dynamic interaction between inflammasome that regulated inflammasome-mediated inflammation in pancreatic adenocarcinoma cells. [Read the Full Post]