Blog of Signaling Pathways

Recurrent Mutations in Cyclin D3 Confer Clinical Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia

566 views | Jun 28 2021

Catherine C Smith et al. thought that Mutations in CCND3, a gene not commonly mutated in AML, were a novel cause of clinical primary resistance to FLT3 inhibitors in AML and might have sensitivity to CDK4/6 inhibition. [Read the Full Post]

Natural history of Waldenström macroglobulinemia following acquired resistance to ibrutinib monotherapy

1149 views | Jun 27 2021

Joshua N Gustine et al. revealed that continuation of ibrutinib until subsequent treatment was associated with improved disease control and clinical outcomes. [Read the Full Post]

Identification of autophagy-related genes as targets for senescence induction using a customizable CRISPR-based suicide switch screen

216 views | Jun 27 2021

Arnout Schepers et al. presented a suicide switch system that allowed genome-wide CRISPR screening in growth-arrested subpopulations by eliminating the proliferating cells during the screen through activation of a suicide switch in proliferating cells. [Read the Full Post]

Prostate Cancer Detected by Choroidal Tumor and Complete Response to Hormonal Therapy: Case Report and Literature Review of 24 Patients With Choroidal Metastasis From Prostate Cancer

305 views | Jun 25 2021

Toshihiko Matsuo et al. found that metastatic choroidal tumors of prostate cancer would show good response to hormonal therapy when the therapy had not been initiated. [Read the Full Post]

Structure-Based Design of A-1293102, a Potent and Selective BCL-X L Inhibitor

247 views | Jun 25 2021

Zhi-Fu Tao et al. thought that A-1293102 represented one of the few distinct structural series of selective BCL-XL inhibitors, and thus served as a useful tool for biological studies as well as a lead compound for further optimization. [Read the Full Post]

Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia

324 views | Jun 24 2021

Ana Colado et al. showed that the IgM/IgA enriched preparation not only affected relevant mechanisms involved in CLL pathogenesis but also had a particular profile of immunomodulatory effects on T cells that deserved further investigation. [Read the Full Post]

PARP and CDK4/6 inhibitor combination therapy induces apoptosis and suppresses neuroendocrine differentiation in prostate cancer

501 views | Jun 24 2021

Cheng Wu et al. provided a molecular rationale for PARPi and CDK4/6i combination therapy and revealed mechanism-based clinical trial opportunities for men with NEPC. [Read the Full Post]

Allosteric Activation of SARS-CoV-2 RNA-Dependent RNA Polymerase by Remdesivir Triphosphate and Other Phosphorylated Nucleotides

553 views | Jun 23 2021

Bing Wang et al. demonstrated that RdRp was allosterically activated by nontemplating phosphorylated nucleotides, including naturally occurring alarmone ppGpp and synthetic remdesivir triphosphate. [Read the Full Post]

A Rho Kinase (ROCK) Inhibitor, Y-27632, Inhibits the Dissociation-Induced Cell Death of Salivary Gland Stem Cells

870 views | Jun 23 2021

Kichul Kim et al. demonstrated the protective effects of Y-27632 against dissociation-induced apoptosis of SGSCs during their culture in vitro. [Read the Full Post]

Inhibition of DNA-PK with AZD7648 Sensitizes Tumor Cells to Radiotherapy and Induces Type I IFN-Dependent Durable Tumor Control

266 views | Jun 22 2021

Kyoko Nakamura et al. found that blocking the NHEJ DNA repair pathway with AZD7648 in combination with RT leaded to durable immune-mediated tumor control. [Read the Full Post]

The KRAS G12C Inhibitor MRTX849 Reconditions the Tumor Immune Microenvironment and Sensitizes Tumors to Checkpoint Inhibitor Therapy

643 views | Jun 22 2021

David M Briere et al. demonstrated KRAS inhibition reversed an immunosuppressive tumor microenvironment and sensitized tumors to CIT through multiple mechanisms. [Read the Full Post]

Ivacaftor-elexacaftor-tezacaftor and tacrolimus combination in cystic fibrosis

567 views | Jun 21 2021

Megan Smith et al. described a pediatric liver transplant recipient with clinical decline related to cystic fibrosis who improved substantially with ETI, without significant impact on the systemic exposure of either ETI or tacrolimus. [Read the Full Post]

Partial Rescue of F508del-CFTR Stability and Trafficking Defects by Double Corrector Treatment

294 views | Jun 21 2021

Valeria Capurro et al. thought that it was still possible to further improve mutant CFTR rescue with the development of corrector combinations having maximal effects on mutant CFTR structural and functional properties. [Read the Full Post]

Flurbiprofen as a biphenyl scaffold for the design of small molecules binding to PD-L1 protein dimer

804 views | Jun 20 2021

Christian Bailly et al. found that the longer FLB derivative HCT1026 appeard as a suitable binder of the PD-L1 dimer, sliding well along the BMS binding cavity. [Read the Full Post]

Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation

639 views | Jun 19 2021

Hyeon Young Park et al. found that treatment with a glutamine antagonist is a promising approach to prevent progression of atherosclerosis and restenosis. [Read the Full Post]

Nonclinical Safety Profile of Sotorasib, a KRAS G12C-Specific Covalent Inhibitor for the Treatment of KRAS p.G12C-Mutated Cancer

141 views | Jun 19 2021

Katsu Ishida et al. found that the nonclinical safety program support a high benefit/risk ratio of sotorasib for the treatment of patients with KRAS p.G12C-mutated tumors. [Read the Full Post]

Binding Insights into Quadruplex Selective Carbazole Ligands

540 views | Jun 18 2021

Diana Müller et al. thought that carbazole was a very promising scaffold for assembling G4 ligands with a range of novel functional applications. [Read the Full Post]

HeLa TI cell-based assay as a new approach to screen for chemicals able to reactivate the expression of epigenetically silenced genes

708 views | Jun 18 2021

Varvara Maksimova et al. showed that N-nitrosodiphenylamine and N-nitrosodimethylamine reactivated epigenetically silenced genes, probably by affecting DNA methylation. [Read the Full Post]

Genetic variant within CDK6 regulates immune response to palbociclib treatment

557 views | Jun 17 2021

Valentina Serra et al. suggested that the effect of palbociclib treatment might depend on underlying genetically encoded individual immune response as well as the direct response to the drug. [Read the Full Post]

Non-hotspot PIK3CA mutations are more frequent in CLOVES than in common or combined lymphatic malformations

209 views | Jun 17 2021

Pascal Brouillard et al. demonstrated efficacy of Sirolimus and Alpelisib in treating patients with an LM or PROS. [Read the Full Post]