Blog of Signaling Pathways

Targeting Glutaminolysis Shows Efficacy in Both Prednisolone-Sensitive and in Metabolically Rewired Prednisolone-Resistant B-Cell Chi

15 views | Aug 29 2023

The study revealed that prednisolone-resistant childhood acute lymphoblastic leukemia (cALL) cells exhibit significant alterations in metabolic pathways, including oxidative phosphorylation, glycolysis, amino acid metabolism, and activation of mTORC1 and MYC signaling, highlighting the potential therapeutic target of inhibiting glutamine metabolism. [Read the Full Post]

Therapeutic inhibition of Bmi-1 ablates chemoresistant cancer stem cells in adenoid cystic carcinoma

75 views | Aug 29 2023

Targeting Adenoid Cystic Carcinoma (ACC) Cancer Stem Cells (CSCs) with Bmi-1 inhibitors, such as PTC596, demonstrates the potential to overcome chemoresistance and prevent tumor relapse in ACC. [Read the Full Post]

Targeting of SOS1: from SOS1 Activators to Proteolysis Targeting Chimeras

78 views | Aug 29 2023

The development of KRAS G12C-directed drugs and SOS1 inhibitors represents promising approaches for targeting mutated oncogenes in lung, pancreatic, and colon cancers. [Read the Full Post]

Protection of Regulatory T Cells from Fragility and Inactivation in the Tumor Microenvironment

101 views | Aug 29 2023

Downregulation of the IFNAR1 chain in intratumoral Treg cells, mediated by p38α kinase, protects them from fragility and maintains their immunosuppressive activities, while targeting sumoylation with the inhibitor TAK981 induces Treg fragility and inhibits tumor growth, offering potential therapeutic approaches for enhancing immunotherapies against cancer. [Read the Full Post]

MEK inhibition sensitizes pancreatic cancer to STING agonism by tumor-cell intrinsic amplification of type I interferon signaling

82 views | Aug 28 2023

MEK inhibitors synergistically enhance the cytotoxic effects of STING agonists on pancreatic ductal adenocarcinoma (PDAC) cells by suppressing NF-κB activation and promoting Type I interferon-dependent cell death. [Read the Full Post]

Corrosion mitigation characteristics of some novel organoselenium thiourea derivatives for acid pickling of C1018 steel via experimental and theoretical study

13 views | Aug 28 2023

DS036 and DS038, two organoselenium thiourea derivatives, demonstrated high inhibition efficiencies and the ability to form a protective layer, effectively preventing corrosion of C-steel in molar HCl. [Read the Full Post]

Efficacy and Safety of Tyrosine Kinase 2/Janus Kinase 1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial

60 views | Aug 28 2023

The phase IIb study showed that brepocitinib at doses of 30 mg and 60 mg once daily (QD) was more effective than placebo in reducing symptoms of psoriatic arthritis (PsA) and demonstrated a favorable safety profile throughout the 52-week study. [Read the Full Post]

Lysosomal lipid peroxidation mediates immunogenic cell death

58 views | Aug 28 2023

The study by Bhardwaj et al. demonstrates that the lysosomal inhibitor DC661 induces lysosomal lipid peroxidation, leading to lysosomal membrane permeabilization, tumor cell death, and subsequent immune-mediated tumor cell clearance, suggesting the potential for combined immunotherapy and lysosomal inhibition in clinical trials. [Read the Full Post]

Inhibiting Histone and DNA Methylation Improves Cancer Vaccination in an Experimental Model of Melanoma

28 views | Aug 28 2023

The study demonstrated that a dual inhibitor targeting histone methyltransferase G9a and DNA methyltransferases (DNMTs) induced tumor cell cycle arrest, apoptosis, and an IFN-I response, while promoting dendritic cell and T-cell infiltration, ultimately increasing the overall survival of mice with melanoma in combination with TCR-redirected T-cell therapy and dendritic cell vaccination. [Read the Full Post]

Angiotensin-(1-7) ameliorates intestinal barrier dysfunction by activating the Keap1/Nrf2/HO-1 signaling pathway in acute pancreatitis

101 views | Aug 27 2023

Ang-(1-7) attenuates acute pancreatitis-induced intestinal inflammation and oxidative injuries by activating the Keap1/Nrf2/HO-1 pathway. [Read the Full Post]

BTK Inhibitors in the Frontline Management of Waldenström Macroglobulinemia

55 views | Aug 27 2023

BTK inhibitors, such as ibrutinib and zanubrutinib, have shown promising results in both treatment-naïve and relapsed/refractory Waldenström macroglobulinemia (WM) patients, with improved response rates and prolonged progression-free survival. [Read the Full Post]

How We Manage Patients with Indolent B-Cell Malignancies on Bruton's Tyrosine Kinase Inhibitors: Practical Considerations for Nurses and Pharmacists

0 views | Aug 27 2023

This paper aims to provide Canadian nurses and pharmacists with a comprehensive reference on dosing, co-administration, and adverse event management strategies for patients with indolent B-cell NHL or CLL undergoing treatment with BTK inhibitors, addressing the evolving treatment landscape and unique safety profiles of these agents. [Read the Full Post]

Effect of erythrophagocytosis-induced ferroptosis during angiogenesis in atherosclerotic plaques

82 views | Aug 27 2023

Intraplaque angiogenesis leads to the release of erythrocytes, their phagocytosis by macrophages, and subsequent erythrophagocytosis-induced ferroptosis, which contributes to plaque destabilization in advanced atherosclerosis and can be prevented by the ferroptosis inhibitor UAMC-3203. [Read the Full Post]

Autophagy regulates transforming growth factor β signaling and receptor trafficking

32 views | Aug 27 2023

Inhibition of autophagy in non-small cell lung cancer cells attenuates pro-tumorigenic TGFβ signaling by impairing receptor trafficking, leading to decreased Smad2/Smad3 phosphorylation and nuclear accumulation. [Read the Full Post]

PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis

62 views | Aug 26 2023

The study identified multidrug-resistant CLL cells in patients and demonstrated that a small molecule activator of PP2A called DT-061 induced apoptosis in these cells independently of Bax/Bak, providing a potential strategy to overcome treatment resistance. [Read the Full Post]

Anticancer effect of zanubrutinib in HER2-positive breast cancer cell lines

68 views | Aug 26 2023

Zanubrutinib, a small molecule Bruton's tyrosine kinase (BTK) inhibitor, has shown potential as an inhibitor of the HER2 signaling pathway and a candidate for repurposing in HER2-positive breast cancer. [Read the Full Post]

Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors

74 views | Aug 26 2023

AZD3229 is a potent and selective small-molecule inhibitor with the potential to be a best-in-class treatment for a broad range of primary and imatinib-resistant secondary mutations in gastrointestinal stromal tumor (GIST). [Read the Full Post]

FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors

34 views | Aug 26 2023

On September 21, 2022, the FDA granted accelerated approval to selpercatinib (Retevmo) for the treatment of adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion, making it the first tissue-agnostic targeted therapy for RET alterations. [Read the Full Post]

Selective Inhibition of Aurora Kinase A by AK-01/LY3295668 Attenuates MCC Tumor Growth by Inducing MCC Cell Cycle Arrest and Apoptosis

40 views | Aug 26 2023

AK-01, a highly selective AURKA inhibitor, demonstrates potent tumor suppression through apoptosis and cell cycle arrest in MCPyV-negative Merkel cell carcinoma cells without RB expression, highlighting its potential as a promising therapeutic option for MCC management. [Read the Full Post]

Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases

98 views | Aug 25 2023

This comprehensive review highlights the structure, biological functions, and therapeutic potential of CLKs and their inhibitors, shedding light on their significance in various human diseases and paving the way for future clinical treatments. [Read the Full Post]