Blog of Signaling Pathways

Small molecule inhibitor RepSox prevented ovariectomy-induced osteoporosis by suppressing osteoclast differentiation and bone resorption

392 views | Mar 22 2020

Mei L et al. suggested that RepSox regulates osteoclast differentiation, bone resorption, and OVX-induced OP via the suppression of the Smad3 and JNK/AP-1 pathways. [Read the Full Post]

Biguanides Induce Acute de novo Lipogenesis in Human Primary Sebocytes

388 views | Mar 22 2020

Nicoll J et al. found that biguanides, isotretinoin and azithromycin induced an acute dose and time-dependent increase in [14C]-acetate labeling of neutral lipids, while AICAR, an AMPK activator, inhibited this DNL response. Biguanides did not activate AMPK in sebocytes, however, they significantly reduced oxygen consumption rate and increased lactate production. Treatment with biguanides, but not isotretinoin, significantly upregulated ACSS2 gene expression in primary sebocytes and showed synergism with lipogenic activators to induce DNL genes. [Read the Full Post]

The impact of dose modification and temporary interruption of ibrutinib on outcomes of chronic lymphocytic leukemia patients in routine clinical practice

417 views | Mar 21 2020

Parikh SA et al. illustrated the challenges associated with continuous oral therapy with ibrutinib in patients with CLL. [Read the Full Post]

Chromatin mapping and single-cell immune profiling define the temporal dynamics of ibrutinib response in CLL

524 views | Mar 21 2020

Rendeiro AF et al. described time-dependent cellular, molecular, and regulatory effects for therapeutic inhibition of B cell receptor signaling in CLL, and it establishes a broadly applicable method for epigenome/transcriptome-based treatment monitoring. [Read the Full Post]

Blocking c-Met and EGFR reverses acquired resistance of PARP inhibitors in triple-negative breast cancer

334 views | Mar 20 2020

Chu YY et al. suggested that combined inhibition of c-MET and EGFR could potentially re-sensitize TNBC to the cytotoxic effects of PARPi. [Read the Full Post]

Inhibition of the erythropoietin-producing receptor EPHB4 antagonizes androgen receptor overexpression and reduces enzalutamide resistance

359 views | Mar 20 2020

Li C et al. provided critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy. [Read the Full Post]

JNJ-26481585 primes rhabdomyosarcoma cells for chemotherapeutics by engaging the mitochondrial pathway of apoptosis

672 views | Mar 19 2020

Heinicke U et al. indicated the second-generation HDACI JNJ-26481585 cooperates with chemotherapeutics to engage mitochondrial apoptosis in RMS cells, demonstrating that JNJ-26481585 represents a promising strategy for chemosensitization of RMS. [Read the Full Post]

LB-100, a novel Protein Phosphatase 2A (PP2A) inhibitor, sensitizes malignant meningioma cells to the therapeutic effects of radiation

398 views | Mar 19 2020

Ho WS et al. provided convincing preclinical data to support the use of LB-100 as a radiosensitizing agent for treatment of malignant meningioma. Its potential for clinical application deserves further investigation. [Read the Full Post]

A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors

456 views | Mar 17 2020

Varga A et al. indicated that GDC-0994 had an acceptable safety profile and pharmacodynamic effects were observed by FDG-PET and in serial tumor biopsies. Single-agent activity was observed in 2 patients with BRAF-mutant colorectal cancer. [Read the Full Post]

The HDAC Inhibitor Quisinostat (JNJ-26481585) Supresses Hepatocellular Carcinoma alone and Synergistically in Combination with Sorafenib by G0/G1 phase arrest and Apoptosis induction

583 views | Mar 17 2020

He B et al. indicated that quisinostat, as a novel chemotherapy for HCC, exhibited excellent antitumor activity in vitro and vivo, which was even enhanced by the addition of sorafenib, implying combination of quisinostat with sorafenib a promising and alternative therapy for patients with advanced hepatocellular carcinoma. [Read the Full Post]

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

467 views | Mar 16 2020

Tian X et al.demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment. [Read the Full Post]

Structure of the intact ATM/Tel1 kinase

509 views | Mar 16 2020

Wang X et al. provided a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents. [Read the Full Post]

Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD)

711 views | Mar 15 2020

Nikonova AS et al. identified a new biologic activity for HSP90 and support a cilia-based mechanism for cyst repression.-Nikonova, A. S., Deneka, A. Y., Kiseleva, A. A., Korobeynikov, V., Gaponova, A., Serebriiskii, I. G., Kopp, M. C., Hensley, H. H., Seeger-Nukpezah, T. N., Somlo, S., Proia, D. A., Golemis, E. A. Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD). [Read the Full Post]

The novel HSP90 inhibitor STA-9090 exhibits activity against Kit-dependent and -independent malignant mast cell tumors

641 views | Mar 15 2020

Lin TY et al. showed that STA-9090 exhibits broad activity against mast cells expressing WT or mutant Kit, suggesting it may be an effective agent in the clinical setting against mast cell malignancies. [Read the Full Post]

WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance

373 views | Mar 14 2020

Zheng H et al. demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. [Read the Full Post]

Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation of RAS/MAPK Signaling

1042 views | Mar 14 2020

Nelson-Taylor SK et al. demonstrated that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation. [Read the Full Post]

ATM induces MacroD2 nuclear export upon DNA damage

553 views | Mar 13 2020

Golia B et al. identified a novel feedback regulation between two crucial DNA damage-induced signaling pathways: ADP-ribosylation and ATM activation. [Read the Full Post]

mbined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet

540 views | Mar 13 2020

Luo F et al. suggested that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages. [Read the Full Post]

PXD101 significantly improves nuclear reprogramming and the in vitro developmental competence of porcine SCNT embryos

661 views | Mar 12 2020

Jin JX et al. demonstrated that PXD101 can significantly improve the in vitro and in vivo developmental competence of porcine SCNT embryos and can enhance their nuclear reprogramming. [Read the Full Post]

How Does Empagliflozin Reduce Cardiovascular Mortality? Insights From a Mediation Analysis of the EMPA-REG OUTCOME Trial

573 views | Mar 12 2020

Inzucchi SE et al. indicated in this exploratory analysis from the EMPA-REG OUTCOME trial, changes in markers of plasma volume were the most important mediators of the reduction in risk of CV death with empagliflozin versus placebo. [Read the Full Post]