Blog of Signaling Pathways

Blocking PD1/PDL1 Interactions Together With MLN4924 Therapy Is a Potential Strategy for Glioma Treatment

380 views | Feb 26 2020

Natalia Filippova et al. concluded that i) PDL1 up-regulation in gliomas and the glioma microenvironment is an important chemotherapeutic target; ii) MLN4924 therapy, combined with a blockage of the PD1/PDL1 pathway, should be considered as a potential strategy for glioma treatment. [Read the Full Post]

The Syk Inhibitor Fostamatinib Disodium (R788) Inhibits Tumor Growth in the Eμ- TCL1 Transgenic Mouse Model of CLL by Blocking Antigen-Dependent B-cell Receptor Signaling

723 views | Feb 26 2020

Mirza Suljagic et al. provided further rationale for clinical trials with R788 in CLL and establish the BCR-signaling pathway as an important therapeutic target in this disease. [Read the Full Post]

Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial

577 views | Feb 25 2020

Basset-Séguin N et al. showed the primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control. [Read the Full Post]

Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma

540 views | Feb 25 2020

McDermott DF et al. suggested that prediction of outcomes with anti-VEGF and immunotherapy may be possible and offer mechanistic insights into how blocking VEGF may overcome resistance to immune checkpoint blockade. [Read the Full Post]

Randomized Trial of Verubecestat for Prodromal Alzheimer's Disease

415 views | Feb 23 2020

Michael F Egan et al. indicated that verubecestat did not improve clinical ratings of dementia among patients with prodromal Alzheimer's disease, and some measures suggested that cognition and daily function were worse among patients who received verubecestat than among those who received placebo. [Read the Full Post]

Crenigacestat, a Selective NOTCH1 Inhibitor, Reduces Intrahepatic Cholangiocarcinoma Progression by Blocking VEGFA/DLL4/MMP13 Axis

1214 views | Feb 23 2020

Serena Mancarella et al. developed and validated a new iCCA PDX model to test in vivo the activity of LY3039478, demonstrating its inhibitory role in Notch-dependent angiogenesis. Thus, the present data provide new knowledge on Notch signaling in iCCA, and support the inhibition of the Notch cascade as a promising strategy for the treatment of this disease. [Read the Full Post]

BACE1 Inhibitor MK-8931 Alters Formation but Not Stability of Dendritic Spines

449 views | Feb 20 2020

Tanja Blume et al. suggested that carefully dosed inhibitors might be therapeutically effective without affecting the structural integrity of excitatory synapses if given at an early disease stage. [Read the Full Post]

Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer

431 views | Feb 20 2020

Kyle C Cuneo et al. indicated that AZD1775 in combination with gemcitabine and radiation therapy was well tolerated at a dose that produced target engagement in a surrogate tissue. The overall survival is substantially higher than prior results combining gemcitabine with radiation therapy and warrants additional investigation. [Read the Full Post]

Repotrectinib (TPX-0005), Effectively Reduces Growth of ALK Driven Neuroblastoma Cells

1406 views | Feb 19 2020

Diana Cervantes-Madrid et al. showed that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Repotrectinib (TPX-0005), Effectively Reduces Growth of ALK Driven Neuroblastoma Cells

0 views | Feb 19 2020

Diana Cervantes-Madrid et al. showed that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Effects of the Preparation Method on the Formation of True Nimodipine SBE-β-CD/HP-β-CD Inclusion Complexes and Their Dissolution Rates Enhancement

1077 views | Feb 18 2020

Farouk Semcheddine et al. showed that all the products exhibited higher dissolution rate than those of the physical mixtures and ND alone, in all mediums. However, the kneading complexes displayed the maximum dissolution rate in comparison with drug and other complexes, confirming the influence of the preparation method on the physicochemical properties of the products. [Read the Full Post]

Rapamycin Combined With MCC950 to Treat Multiple Sclerosis in Experimental Autoimmune Encephalomyelitis

743 views | Feb 18 2020

Ling Xu et al. provided theoretical support to the therapeutic evaluation of RAPA and MCC950 to make the mammalian targets of RAPA and NLRP3 the therapeutic targets of MS. [Read the Full Post]

AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK

537 views | Feb 17 2020

Yadav AK et al. demonstrated that AZD1208 inhibits growth of liposarcoma cells and that this activity is mediated through Pim-3 kinase, STAT-3, mTOR, S6 and AMPK expression and phosphorylation pathways. [Read the Full Post]

Targeting KRAS Mutant Cancers With a Covalent G12C-Specific Inhibitor

433 views | Feb 17 2020

Matthew R Janes et al. provided in vivo evidence that mutant KRAS can be selectively targeted and reveals ARS-1620 as representing a new generation of KRASG12C-specific inhibitors with promising therapeutic potential. [Read the Full Post]

Administration of Lapatinib with Food Increases Its Plasma Concentration in Chinese Patients with Metastatic Breast Cancer: A Prospective Phase II Study

596 views | Feb 16 2020

Xu F et al. showed that receiving lapatinib with food can increase its plasma concentration with no significantly increased drug-related toxicity. We suggest that a larger-sample-size clinical trial is needed to fully understand the effect of administration of lapatinib with food. [Read the Full Post]

Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery

0 views | Feb 16 2020

Colclough N et al. demonstrated how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders. [Read the Full Post]

Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition

472 views | Feb 14 2020

Hong AL et al. identified a synthetic lethal relationship between SMARCB1-deficient cancers and reliance on the UPS which provides the foundation for a mechanism-informed clinical trial with proteasome inhibitors. [Read the Full Post]

Multiple myeloma with 1q21 amplification is highly sensitive to MCL-1 targeting

359 views | Feb 14 2020

Slomp A et al. indicated that amplification of 1q21 identifies an MM subset highly sensitive to MCL-1 inhibitor treatment and can be used as a predictive marker to guide selection of therapy. [Read the Full Post]

RIP3 inhibition protects locomotion function through ameliorating mitochondrial antioxidative capacity after spinal cord injury

0 views | Feb 13 2020

Wang Y et al. suggested improving antioxidative capacity as a potential multifunctional treatment after SCI and the broader possibility of targeting RIP3 activity as a therapeutic window for spinal neuroprotective intervention. [Read the Full Post]

L-Cystathionine Protects against Homocysteine-Induced Mitochondria-Dependent Apoptosis of Vascular Endothelial Cells

296 views | Feb 13 2020

Wang X et al. indicated that L-cystathionine could protect against homocysteine-induced mitochondria-dependent apoptosis of HUVECs. [Read the Full Post]