Blog of Signaling Pathways

The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL

814 views | Apr 13 2019

Savino AM et al. indicated givinostat killed ruxolitinib-resistant cells and potentiated the effect of current chemotherapy. Thus, givinostat in combination with conventional chemotherapy may represent an effective therapeutic option for these difficult-to-treat subsets of ALL. Lastly, the selective killing of cancer cells by givinostat may allow the design of reduced intensity regimens in CRLF2-rearranged Down syndrome-associated BCP-ALL patients with an overall benefit in terms of both toxicity and related complications. [Read the Full Post]

CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells

813 views | Apr 13 2019

Silva-Pavez E et al. suggested that an aberrantly elevated expression/activity of CK2 may play a key role in CRC, promoting cell viability and proliferation in untreated cells, however, its inhibition with silmitasertib promotes methuosis-like cell death associated to massive catastrophic vacuolization, accounting for decreased tumorigenicity at later times. These characteristics of silmitasertib support a potential therapeutic use in CRC patients and probably other CK2-dependent cancers. [Read the Full Post]

Combining Smoothened Agonist and NEL-Like Protein-1 Enhances Bone Healing

710 views | Apr 12 2019

Lee S et al. suggested that combining the hedgehog signaling agonist SAG and NELL-1 has potential as a novel therapeutic strategy for the healing of critical-size bone defects. Future directions will include optimization of dosage and delivery strategy for an SAG and NELL-1 combination product. [Read the Full Post]

Chemoproteomic Selectivity Profiling of PIKK and PI3K Kinase Inhibitors

402 views | Apr 12 2019

Reinecke M et al. showed that NVP-BEZ235 is not a PI3K inhibitor. Surprisingly, the designated ATM inhibitor CP466722 was found to bind strongly to ALK2, identifying a new chemotype for drug discovery to treat fibrodysplasia ossificans progressiva. [Read the Full Post]

Copanlisib: First Global ApprovalMarkham A

411 views | Apr 11 2019

Markham A had summarize the milestones in the development of copanlisib leading to this first approval for relapsed follicular lymphoma. [Read the Full Post]

Napabucasin: An Update on the First-in-Class Cancer Stemness Inhibitor

768 views | Apr 11 2019

Hubbard JM et al. showed that napabucasin may prove useful in targeting cancer stem cells, with the potential to suppress metastasis and prevent relapse in patients with varying cancer types. [Read the Full Post]

lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling

0 views | Apr 10 2019

Lu Y et al. described a double-negative feedback loop between MIR100HG and the transcription factor GATA6, whereby GATA6 represses MIR100HG, but this repression is relieved by miR-125b targeting of GATA6. These findings identify a clinically actionable, epigenetic cause of cetuximab resistance. [Read the Full Post]

ICG-001 suppresses growth of gastric cancer cells and reduces chemoresistance of cancer stem cell-like population

615 views | Apr 10 2019

Liu Y et al. suggested that ICG-001 suppresses GC cell line growth, metastasis and reduces its stem cell-like properties and chemoresistance, indicating that ICG-001 is a potentially useful small molecule therapeutic for GC. [Read the Full Post]

Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial

488 views | Apr 09 2019

Moore KN et al. identified no new safety signals. Our data support expansion of the treatment indication for poly(ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations. [Read the Full Post]

Exploration of MST1-Mediated Secondary Brain Injury Induced by Intracerebral Hemorrhage in Rats via Hippo Signaling Pathway

450 views | Apr 09 2019

Zhang P et al. revealed that MST1 played an important role in the SBI following ICH, and inhibition of MST1 could alleviate ICH-induced SBI. Therefore, MST1 may be considered as a potential therapeutic target for SBI following ICH. [Read the Full Post]

Protection of Mcc950 against high-glucose-induced human retinal endothelial cell dysfunction

506 views | Apr 08 2019

Zhang Y et al indicated Mcc950 inhibited HREC dysfunction under high-glucose conditions and this research may offer insight for future pharmaceutical approaches for treating DR. [Read the Full Post]

Lipoxygenase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3

388 views | Apr 08 2019

Shintoku R et al suggested that tumor ferroptosis is promoted by LOX-catalyzed lipid hydroperoxide generation in cellular membranes. [Read the Full Post]

MicroRNA-496 and Mechanistic Target of Rapamycin Expression are Associated with Type 2 Diabetes Mellitus and Obesity in Elderly People

410 views | Apr 06 2019

Rubie C et al. concluded that mTOR signaling through TORC1 may be affected in the regulation of T2DM. [Read the Full Post]

Bcl-xL inhibition enhances Dinaciclib-induced cell death in soft-tissue sarcomas

444 views | Apr 05 2019

Rello-Varona S et al showed that Bcl-xL inhibitor A-1331852 also synergized with conventional chemotherapy drugs as Gemcitabine. Thus, Bcl-xL targeted therapy arises as a major opportunity to the treatment of STS. [Read the Full Post]

Memantine and Q-VD-OPh Treatments in Experimental Spinal Cord Injury: Combined Inhibition of Necrosis and Apoptosis

596 views | Apr 05 2019

Aydoseli A et al showed that combined use of memantine and Q-VD-OPh provides better histological and clinical results. The combined inhibition of the two major pathways, necrosis and apoptosis, needs to be further assessed with in-vivo or in-vitro studies. [Read the Full Post]

Oncogenic role of ABHD5 in endometrial cancer

666 views | Apr 04 2019

Zhou Q suggested that ABHD5 may play an oncogenic role in endometrial cancer via the AKT pathway. [Read the Full Post]

Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction

341 views | Apr 04 2019

Walaszczyk A et al. provided proof-of-concept evidence that senescent cells are major contributors to impaired function and increased mortality following MI and that senolytics are a potential new therapeutic avenue for MI. [Read the Full Post]

Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial

561 views | Apr 03 2019

Planchard D et al. found that Dabrafenib plus trametinib represents a new therapy with clinically meaningful antitumour activity and a manageable safety profile in patients with previously untreated BRAFV600E-mutant NSCLC. [Read the Full Post]

White light emitting diode induces autophagy in hippocampal neuron cells through GSK-3-mediated GR and RORα pathways

633 views | Apr 03 2019

Yang Y et al. demonstrated that GSK-3-mediated GR/RORα signaling pathway is involved in white LED light-induced autophagy in hippocampal neuron cells. [Read the Full Post]

MCL-1 or BCL-xL-dependent resistance to the BCL-2 antagonist (ABT-199) can be overcome by specific inhibitor as single agents and in combination with ABT-199 in acute myeloid leukemia cells

322 views | Apr 02 2019

Wang Q et al. showed that ABT-199 could synergize with A-1210477 in vitro or in vivo. [Read the Full Post]