Category

Archives

Blog of Signaling Pathways

The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models

331 views | Nov 02 2019

Zhang S et al. provided the molecular basis for the promising activity being observed in ALK+, crizotinib-resistant patients with NSCLC being treated with brigatinib in clinical trials. [Read the Full Post]

FoxO1 regulates myocardial glucose oxidation rates via transcriptional control of pyruvate dehydrogenase kinase 4 expression

143 views | Nov 02 2019

Gopal K et al. demonstrated that pyruvate dehydrogenase kinase 4 is a direct transcriptional target of FoxO1 (but not FoxO3/FoxO4) in the heart. Furthermore, we report here, for the first time, that FoxO1 inhibition increases glucose oxidation in the isolated working mouse heart. [Read the Full Post]

Nutlin-3 enhances the bortezomib sensitivity of p53-defective cancer cells by inducing paraptosis

203 views | Nov 01 2019

Lee DM et al. suggested that bortezomib/nutlin-3 perturbs proteostasis, triggering ER/mitochondria stress and irrecoverable impairments in their structure and function, ultimately leading to paraptotic cell death. [Read the Full Post]

AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules

0 views | Nov 01 2019

Guichard SM et al. indicated the ability to dose AZD2014 intermittently, together with its ability to block signaling from both mTORC1 and mTORC2 complexes, makes this compound an ideal candidate for combining with endocrine therapies in the clinic. AZD2014 is currently in phase II clinical trials. [Read the Full Post]

SP600125 suppresses Keap1 expression and results in NRF2-mediated prevention of diabetic nephropathy

216 views | Oct 30 2019

Zhang H et al. demonstrated that NRF2 is required for SP600125's protection against DN. SP600125 activates NRF2 possibly via inhibition of JNK-induced Keap1 expression. [Read the Full Post]

Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model

168 views | Oct 30 2019

Cheng NT et al. demonstrated that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA.Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model. [Read the Full Post]

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours

0 views | Oct 29 2019

Xu H et al. indicated these data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. CX-5461 is now in advanced phase I clinical trial for patients with BRCA1/2 deficient tumours (Canadian trial, NCT02719977, opened May 2016). [Read the Full Post]

Nutlin-3a selects for cells harbouring TP53 mutations

0 views | Oct 29 2019

Kucab JE et al. suggested that including a Nutlin-3a counter-screen significantly improves the specificity and efficiency of the HIMA, whereby TP53-mutated clones are selected prior to sequencing and TP53-WT clones can be discarded. [Read the Full Post]

NVP-BKM120 inhibits colon cancer growth via FoxO3a-dependent PUMA induction

0 views | Oct 28 2019

Yang S et al. demonstrated a key role of PUMA in mediating the anticancer effects of NVP-BKM120 and suggest that PUMA could be used as an indicator of NVP-BKM120 sensitivity, and also have important implications for it clinical applications. [Read the Full Post]

TAZ promotes the proliferation and osteogenic differentiation of human periodontal ligament stem cells via the p-SMAD3

204 views | Oct 28 2019

Gu K et al. indicated that Hippo/TAZ plays a positive role inside the proliferation, stemness maintenance, and osteogenic specialization of h-PDLSCs, and the specific downstream factor of osteogenic differentiation is SMAD3. [Read the Full Post]

Nuclear localization of β-catenin and expression of target genes are associated with increased Wnt secretion in oral dysplasia

499 views | Oct 27 2019

Reyes M et al. indicated that secretion of Wnt ligands is critical for β-catenin nuclear localization and expression of target genes in oral dysplasia. [Read the Full Post]

Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial

173 views | Oct 25 2019

Baselga J et al. showed that PI3K inhibition combined with endocrine therapy is effective in postmenopausal women with endocrine-resistant, hormone receptor-positive and HER2-negative advanced breast cancer. Use of more selective PI3K inhibitors, such as α-specific PI3K inhibitor, is warranted to further improve safety and benefit in this setting. No further studies are being pursued because of the toxicity associated with this combination. [Read the Full Post]

BKM120 induces apoptosis and inhibits tumor growth in medulloblastoma

146 views | Oct 25 2019

Zhao P et a. indicated that these findingshelp to establish a basis for clinical trials of BKM120, which could be a novel therapy for the treatment of medulloblastoma patients. [Read the Full Post]

RBBP8/CtIP suppresses P21 expression by interacting with CtBP and BRCA1 in gastric cancer

221 views | Oct 24 2019

Yu Y et al. revealed the chromatin modification role of RBBP8, which could suppress the histone acetylation level of P21 promoter by recruiting CtBP co-repressor complex to BRCA1 binding site. [Read the Full Post]

The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia

0 views | Oct 24 2019

Brumatti G et al. demonstrated antileukemic efficacy and safety of the birinapant/emricasan combination in vivo suggest that induction of necroptosis warrants clinical investigation as a therapeutic opportunity in AML. [Read the Full Post]

The PI3K inhibitor GDC-0941 enhances radiosensitization and reduces chemoresistance to temozolomide in GBM cell lines

136 views | Oct 22 2019

Shi F et al. suggested that the combination of TMZ, IR, and GDC-0941 is a promising choice for future treatments of GBM. [Read the Full Post]

Trichostatin A and 5-Aza-2'-Deoxycytidine influence the expression of cold-induced genes in Arabidopsis

263 views | Oct 22 2019

Song Y et al. showed this result will advance our understanding of plant freezing responses and may provide a helpful strategy for cold tolerance improvement in crops. [Read the Full Post]

Exogenous mesenchymal stem cells affect the function of endogenous lung stem cells (club cells) in phosgene-induced lung injury

0 views | Oct 21 2019

Ye K et al. showed that MSCs reduced the secretion of club cells. And MSCs enhanced the proliferation of club cells partly via activating the Notch signaling pathway, which promoted lung injury repair. [Read the Full Post]

The Phosphatidylinositol 3-Kinase Pathway as a Potential Therapeutic Target in Bladder Cancer

110 views | Oct 21 2019

Zeng SX et al. provided new insights into the therapeutic potential of targeting the PI3K pathway for the treatment of bladder cancer. [Read the Full Post]

Prolonged Idasanutlin (RG7388) Treatment Leads to the Generation of p53-Mutated Cells

141 views | Oct 20 2019

Skalniak L et al. showed that although idasanutlin presents much improved activities compared to its precursor, it displays the similar weaknesses, which are limited elimination of cancer cells and the generation of p53-mutated drug-resistant subpopulations. [Read the Full Post]