Blog of Signaling Pathways

PARP and PARG Inhibitors in Cancer Treatment

94 views | May 28 2020

Dea Slade highlighted clinical performance of four PARP inhibitors used in cancer therapy (olaparib, rucaparib, niraparib, and talazoparib) and discussed the predictive biomarkers of inhibitor sensitivity, mechanisms of resistance as well as the means of overcoming them through combination therapy. [Read the Full Post]

MG-132 Attenuates Cardiac Deterioration of Viral Myocarditis via AMPK Pathway

86 views | May 28 2020

Xin-Min Zhang et al. found that MG-132 modulated apoptosis and inflammation, improved hemodynamics, and inhibited the structural remodeling of ventricles in a myocarditis mouse model via regulation of the AMPK signal pathway. [Read the Full Post]

Hypoxia Upregulates Cxcl12 in Hepatocytes by a Complex Mechanism Involving Hypoxia-Inducible Factors and Transforming Growth Factor-β

90 views | May 27 2020

Jenna Strickland et al. demonstrated that hypoxia upregulated Cxcl12 in primary mouse hepatocytes by a mechanism that involved HIFs and TGF-β. [Read the Full Post]

Talazoparib in Patients With a Germline BRCA-Mutated Advanced Breast Cancer: Detailed Safety Analyses From the Phase III EMBRACA Trial

99 views | May 27 2020

Sara A Hurvitz et al. found that Talazoparib was associated with superior efficacy, favorable PROs, and lower HRU rate versus chemotherapy in gBRCA-mutated ABC. Toxicities were manageable with talazoparib dose modification and supportive care. [Read the Full Post]

GSK1120212 (JTP-74057) Is an Inhibitor of MEK Activity and Activation With Favorable Pharmacokinetic Properties for Sustained in Vivo Pathway Inhibition

0 views | May 26 2020

Aidan G Gilmartin et al. found that GSK1120212 combineed high potency, selectivity, and long circulating half-life, offering promise for successfully targeting the narrow therapeutic window anticipated for clinical MEK inhibitors. [Read the Full Post]

Inhibition of Apoptosis by Caspase Inhibitor Z-VAD-FMK Improves Cryotolerance of in Vitro Derived Bovine Embryos

0 views | May 26 2020

Maria Elena Pero et al. found that the addition of 20 μM Z-VAD-FMK during vitrification/warming and post-warming culture partially inhibited cryopreservation-induced apoptosis by reducing the level of active caspase 3, suggesting a potential used as an additive to ameliorate the efficiency of embryo cryopreservation in cattle, critical for a further diffusion of IVEP technology in the field. [Read the Full Post]

Axl Inhibitor R428 Induces Apoptosis of Cancer Cells by Blocking Lysosomal Acidification and Recycling Independent of Axl Inhibition

74 views | May 25 2020

Fangfang Chen et al. uncovered a novel function and mechanism of R428 in addition to its ability to inhibit Axl. [Read the Full Post]

Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor-Sensitive and -Resistant Chronic Myeloid Leukemia

0 views | May 25 2020

Isabel Ben-Batalla et al. showed that Axl inhibition had therapeutic potential in BCR-ABL TKI-sensitive as well as resistant CML and support the need for clinical trials. [Read the Full Post]

Essential Thrombocythemia Treatment Algorithm 2018

168 views | May 24 2020

Ayalew Tefferi et al. provided a point-of-care treatment algorithm that was risk-adapted and based on evidence and decades of experience. [Read the Full Post]

Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island

0 views | May 24 2020

Sebastian I Arriola Apelo et al. discussed recent advances in understanding the molecular and physiological effects of rapamycin treatment, and they discussed how the use of alternative rapamycin treatment regimens or rapamycin analogs had the potential to mitigate the deleterious side effects of rapamycin treatment by more specifically targeting mTORC1. [Read the Full Post]

Early Long-Term Administration of the CSF1R Inhibitor PLX3397 Ablates Microglia and Reduces Accumulation of Intraneuronal Amyloid, Neuritic Plaque Deposition and Pre-Fibrillar Oligomers in 5XFAD Mouse Model of Alzheimer

66 views | May 22 2020

Justyna Sosna et al. demonstrate that CSF1R signaling, either directly on neurons or mediated by microglia, was crucial for the accumulation of intraneuronal amyloid and formation of neuritic plaques, suggesting that these two events were serially linked in a causal pathway leading to neurodegeneration and neuritic plaque formation. [Read the Full Post]

CHIR-99021 Regulates Mitochondrial Remodelling via β-Catenin Signalling and miRNA Expression During Endodermal Differentiation

0 views | May 22 2020

Yuejiao Ma et al. demonstrated that CHIR-99021 played a role in mitochondrial structure and function remodelling via activation of the β-catenin signalling pathway and inhibited the expression of miRNAs during definitive endodermal differentiation. [Read the Full Post]

Palbociclib (PD0332991)-a Selective and Potent Cyclin-Dependent Kinase Inhibitor: A Review of Pharmacodynamics and Clinical Development

0 views | May 21 2020

Amy S Clark et al. found that Palbociclib was well tolerated and had therapeutic potential for multiple cancers, including breast cancer, where its efficacy had been demonstrated alone and in combination with endocrine therapy. [Read the Full Post]

Pexidartinib: First Approval

85 views | May 21 2020

Yvette N Lamb et al. summarized the milestones in the development of pexidartinib leading to its first approval for TGCT. [Read the Full Post]

ABT-263 Exhibits Apoptosis-Inducing Potential in Oral Cancer Cells by Targeting C/EBP-homologous Protein

93 views | May 20 2020

In-Hyoung Yang et al. provided evidence that ABT-263 may serve as an effective therapeutic agent for the treatment of human oral cancer. [Read the Full Post]

Effects of PCI-32765 and Dasatinib on the Acute Lymphoblastic Leukemic Cells and Their Mechanisms

100 views | May 20 2020

Yuan Deng et al. found that PCI-32765 or Dasatinib could inhibit the proliferation and induced the apoptosis of Sup-B15 and RS4;11 cells, PCI-32765 and Dasatinib displayed the synergistic effects. The possible mechanismmight be related with the blocking of B cell receptor(BCR) signal pathway, thereby inhibiting the cell proliferation and promoting the cell apoptosis. [Read the Full Post]

Low-Dose Enzalutamide in Late-Elderly Patients (≥ 75 Years Old) Presenting With Metastatic Castration-Resistant Prostate Cancer.

64 views | May 19 2020

Vinh-Hung V et al. found that Low-dose enzalutamide in very old, symptomatic, poor-performance patients with metastatic disease was associated with high response rate and survival comparable to standard dose. [Read the Full Post]

Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic.

0 views | May 19 2020

Galiana I et al. supported targeted senolysis as a new therapeutic opportunity to improve outcomes in breast cancer patients [Read the Full Post]

Cerebrospinal fluid penetration of the colony-stimulating factor-1 receptor (CSF-1R) inhibitor, pexidartinib

87 views | May 18 2020

Shankarappa PS et al. found that pexidartinib was well-tolerated in NHPs, with no Grade 3 or Grade 4 toxicities. The CSF penetration of pexidartinib after single-dose oral administration to NHPs was limited. [Read the Full Post]

Discovery of suppressors of CRMP2 phosphorylation reveals compounds that mimic the behavioral effects of lithium on amphetamine-induced hyperlocomotion

90 views | May 18 2020

Zhao WN et al. not only provided insights into the neural substrates regulated by lithium, but also provided novel human neuronal assays for supporting the development of mechanism-based therapeutics for BD and related neuropsychiatric disorders. [Read the Full Post]