Blog of Signaling Pathways

AKT Antagonist AZD5363 Influences Estrogen Receptor Function in Endocrine-Resistant Breast Cancer and Synergizes with Fulvestrant (ICI182780) In Vivo

431 views | Feb 12 2020

Ribas R et al. supported the combination of AZD5363 with fulvestrant as a potential therapy for breast cancer that is sensitive or resistant to E-deprivation or tamoxifen and that activated AKT is a determinant of response, supporting the need for clinical evaluation. [Read the Full Post]

The JAK2 inhibitor AZD1480 inhibits hepatitis A virus replication in Huh7 cells

725 views | Feb 12 2020

Jiang X et al. proposed that AZD1480 can inhibit HAV IRES activity and HAV replication through the inhibition of the La protein. [Read the Full Post]

MiR-509-3 augments the synthetic lethality of PARPi by regulating HR repair in PDX model of HGSOC

452 views | Feb 11 2020

Sun C found that MiR-509-3 can sensitize ovarian cancer cells to Olaparib by impeding HR, which makes it a potential target in PARPi synergistic treatment. [Read the Full Post]

Venetoclax in acute myeloid leukemia - current and future directions

360 views | Feb 11 2020

Lachowiez C et al. provided biological and clinical rationale for current venetoclax based treatments in AML, addresses common adverse events encountered with venetoclax based therapy, and explores emerging clinical data regarding combinations of novel targeted therapeutics used in conjunction with venetoclax for the treatment of AML. [Read the Full Post]

Rho-kinase ROCK inhibitors reduce oligomeric tau protein

1058 views | Feb 10 2020

Hamano T et al. suggested that ROCK inhibitors represent a viable therapeutic route to reduce the pathogenic forms of tau protein in tauopathies, including Alzheimer's disease. [Read the Full Post]

Synergistic lethality between PARP-trapping and alantolactone-induced oxidative DNA damage in homologous recombination-proficient cancer cells

410 views | Feb 10 2020

Wang H found that PARP trapping combined with specific pro-oxidative agents may provide safe and effective ways to broaden the therapeutic potential of PARP inhibitors. [Read the Full Post]

Skin toxicity and efficacy of sunitinib and sorafenib in metastatic renal cell carcinoma: a national registry-based study

388 views | Feb 09 2020

Poprach A et al. found that the presence of skin toxicity is associated with improved OS and PFS in patients with mRCC treated with sunitinib. [Read the Full Post]

The histone deacetylase inhibitor romidepsin spares normal tissues while acting as an effective radiosensitiser in bladder tumours in vivo

612 views | Feb 09 2020

Paillas S et al. demonstrated that romidepsin is an effective radiosensitiser in vitro and in vivo and does not increase the acute and late toxicity after ionising radiation. [Read the Full Post]

The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

385 views | Feb 08 2020

Timm KN et al. introduced different agents known to activate AMPK (metformin, statins, resveratrol, thiazolidinediones, AICAR, specific AMPK activators) as well as exercise and dietary restriction, and discussed the existing evidence for their potential role in cardioprotection from doxorubicin cardiotoxicity. [Read the Full Post]

Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive Her2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

316 views | Feb 08 2020

Demir A et al. demonstrated that the efficacy of palbociclib among heavily treated hormone receptor-positive/HER2-negative advanced BC patients was acceptable clinical benefit, and it was generally well tolerated among this population. [Read the Full Post]

Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib

892 views | Feb 07 2020

Casavecchia G et al. reported and discussed most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. [Read the Full Post]

Role of H3K18ac-regulated nucleotide excision repair-related genes in arsenic-induced DNA damage and repair of HaCaT cells

632 views | Feb 07 2020

Zhang AL et al. provided new ideas for understanding the molecular mechanisms underlying arsenic-induced skin damage. [Read the Full Post]

G250 Antigen-Targeting Drug-Loaded Nanobubbles Combined with Ultrasound Targeted Nanobubble Destruction: A Potential Novel Treatment for Renal Cell Carcinoma

285 views | Feb 06 2020

Yu Z et al. indicated that the combined G250-TNBs and UTND treatment can deliver anti-tumor drugs to local areas of RCC, increase the local effective drug concentration, and enhance anti-tumor efficacy, thus providing a potential novel method for targeted therapy of RCC. [Read the Full Post]

Rapamycin ester analog CCI-779/Temsirolimus alleviates tau pathology and improves motor deficit in mutant tau transgenic mice

331 views | Feb 06 2020

Frederick C et al. indicated that stimulation of mTOR dependent autophagy by CCI-779 compound is efficient to counteract the accumulation of abnormal tau when administered early or late in a tauopathy model and to improve a motor deficit when started before onset of motor signs. [Read the Full Post]

Anticancer drug candidate CBL0137, which inhibits histone chaperone FACT, is efficacious in preclinical orthotopic models of temozolomide-responsive and -resistant glioblastoma

417 views | Feb 05 2020

Barone TA et al. indicated that CBL0137 targets GBM according to its proposed mechanism of action, crosses the blood-brain barrier, and is efficacious in both TMZ-responsive and -resistant orthotopic models, making it an attractive new therapy for GBM. [Read the Full Post]

Proteomic Analysis of an Induced Pluripotent Stem Cell Model Reveals Strategies to Treat Juvenile Myelomonocytic Leukemia

529 views | Feb 05 2020

Pearson S et al. demonstrated these small molecular inhibitors, JQ1 and CBL0137, preferentially extinguish primitive hematopoietic cells from sporadic JMML patients as opposed to cells from healthy individuals. [Read the Full Post]

CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant

474 views | Feb 04 2020

Sakamoto H et al. supported the potential for clinical evaluation of CH5424802 for the treatment of patients with ALK-driven tumors. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

0 views | Feb 04 2020

Svoboda LK et al. demonstrated that the SSP is highly active in Ewing sarcoma and that its oncogenic activation is maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]

Protein tyrosine kinase 2: a novel therapeutic target to overcome acquired EGFR-TKI resistance in non-small cell lung cancer

584 views | Feb 03 2020

Tong X et al. suggested that this combination therapy may be a viable option to overcome EGFR-TKI resistance in NSCLC. [Read the Full Post]

PD98059 protects the brain against mitochondrial-mediated apoptosis and autophagy in a cardiac arrest rat model

400 views | Feb 03 2020

Zheng JH et al. showed that PD98059 decreased the openings of MPTP, CytC release, caspase3 activation, apoptotic indices, LC3-II, Beclin-1and increased P62. PD98059 also inhibited mitochondria-dependent apoptosis and the activity of autophagy in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. The generation of phosphorylated Drp1-616 was down-regulated accompanied by a decrease of TUNEL-positive cells and LC3 in dual immunostaining after PD98059 inhibited activation of ERK signaling pathway in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. [Read the Full Post]