Blog of Signaling Pathways

Molecular alterations and poziotinib efficacy, a pan-HER inhibitor, in human epidermal growth factor receptor 2 (HER2)-positive breast cancers: Combined exploratory biomarker analysis from a phase II clinical trial of poziotinib for refractory HER2-positive breast cancer patients

507 views | Mar 11 2020

Koga T et al. identified HER2 CN amplification, PIK3CA pathway alteration, and ERBB3 cytoplasmic mutation showed predictive roles on clinical outcomes of HER2-positive MBC treated with poziotinib. [Read the Full Post]

Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study

659 views | Mar 11 2020

O'Connor OA et al. showed that monotherapy with belinostat produced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across the major subtypes, irrespective of number or type of prior therapies. These results have led to US Food and Drug Administration approval of belinostat for this indication. [Read the Full Post]

Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro study

606 views | Mar 10 2020

Koga T et al. identified the secondary C805S at the covalent binding site of HER2 to poziotinib as a potential mechanism of acquired resistance. HSP90 inhibitors might be a therapeutic strategy for the C805S secondary mutation. [Read the Full Post]

Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis

912 views | Mar 09 2020

Torres-Hernandez A et al. suggested that SYK is an attractive target for experimental therapeutics in treating hepatic fibrosis and oncogenesis. [Read the Full Post]

The Role and Mechanism of CRT0066101 as an Effective Drug for Treatment of Triple-Negative Breast Cancer

797 views | Mar 09 2020

Liu Y et al. indicated that PRKD inhibitor CRT0066101 exhibits anti-TNBC effects via modulating a phosphor-signaling network and inhibiting the phosphorylation of many cancer-driving factors, including MYC, MAPK1/3, AKT, YAP, and CDC2, providing insight into the important roles as well as the molecular mechanism of CRT0066101 as an effective drug for TNBC. [Read the Full Post]

MGCD0103, a selective histone deacetylase inhibitor, coameliorates oligomeric Aβ25-35 -induced anxiety and cognitive deficits in a mouse model

1784 views | Mar 08 2020

Huang HJ et al. revealed MGCD0103 could be a potential therapeutic agent against AD. [Read the Full Post]

Simultaneous inhibition of JAK and SYK kinases ameliorates chronic and destructive arthritis in mice

432 views | Mar 08 2020

Llop-Guevara A et al. showed that concurrent JAK + SYK inhibition resulted in higher efficacy than single kinase inhibition and TNF blockade in a chronic and severe arthritis model. Thus, blockade of multiple immune signals with dual JAK + SYK inhibition represents a reasonable therapeutic strategy for RA, in particular in patients with inadequate responses to current treatments. Our data supports the multiplicity of events underlying this heterogeneous and complex disease. [Read the Full Post]

An Ilomastat-CD Eye Drop Formulation to Treat Ocular Scarring

430 views | Mar 06 2020

Mohamed-Ahmed AHA et al. showed that Ilomastat-CD has the potential to be formulated as an eye drop for use as an antifibrotic, which may have implications for the prevention of scarring in many settings, for example glaucoma filtration surgery. [Read the Full Post]

The class I/IV HDAC inhibitor mocetinostat increases tumor antigen presentation, decreases immune suppressive cell types and augments checkpoint inhibitor therapy

603 views | Mar 06 2020

Briere D et al. provided evidence that mocetinostat modulates immune-related genes in tumor cells as well as immune cell types in the tumor microenvironment and enhances checkpoint inhibitor therapy. [Read the Full Post]

Precision-cut lung slices from bleomycin treated animals as a model for testing potential therapies for idiopathic pulmonary fibrosis

430 views | Mar 04 2020

Cedilak M et al. suggested that PCLS may be a suitable in vitro model for compound testing during drug development process. [Read the Full Post]

Evaluation of the dopamine β-hydroxylase (DβH) inhibitor nepicastat in participants who meet criteria for cocaine use disorder

795 views | Mar 04 2020

De La Garza R 2nd et al. indicated that nepicastat is safe when co-administered with cocaine and may suppress its positive subjective effects, and may be viable as a pharmacotherapy for treatment of cocaine use disorder. [Read the Full Post]

Inhibitory effect of 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H - imidazole on HCMV DNA replication and permissive infection

298 views | Mar 03 2020

Johnson RA et al. described FHPI as a novel anti-HCMV compound that inhibits synthesis/activation of cellular and/or viral factors required for initiation of HCMV DNA replication. [Read the Full Post]

The DOT1L inhibitor Pinometostat decreases the host-response against infections: Considerations about its use in human therapy

610 views | Mar 03 2020

Marcos-Villar Let al. supported a possible increased vulnerability to infection in MLL-r leukemia patients undergoing pinometostat treatment. Close follow up of infection should be considered in pinometostat therapy to reduce some severe side effects during the treatment. [Read the Full Post]

Phase I Dose-Escalation Study of the pan-HER Inhibitor, PF299804, in Patients With Advanced Malignant Solid Tumors

535 views | Mar 02 2020

Pasi A Jänne et al. showed the MTD of PF299804 is 45 mg/d. Both continuous and intermittent treatment schedules were well tolerated, and encouraging signs of antitumor activity were observed in gefitinib/erlotinib treated NSCLC patients. [Read the Full Post]

T-cell death-associated gene 8 accelerates atherosclerosis by promoting vascular smooth muscle cell proliferation and migration

652 views | Mar 02 2020

Chen LD et al. demonstrated that Tdag8 mediated phenotype transformation, proliferation and migration of VSMCs via the cAMP/PKA signaling pathway, thus partially contributing to atherosclerosis. [Read the Full Post]

The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity Against Acute Lymphoblastic Leukemia

368 views | Mar 01 2020

Thomas Vercruysse et al. showed that KPT-8602 is highly specific for XPO1 inhibition and demonstrates potent anti-leukemic activity supporting clinical application of the second-generation SINE compound for the treatment of ALL. [Read the Full Post]

URMC-099 Facilitates Amyloid-β Clearance in a Murine Model of Alzheimer's Disease

1129 views | Mar 01 2020

Tomomi Kiyota et al. indicated that URMC-099 facilitates Aβ clearance in the brain of APP/PS1 mice. The multifaceted immune modulatory and neuroprotective roles of URMC-099 make it an attractive candidate for ameliorating the course of AD. This is buttressed by removal of pathologic Aβ species and restoration of the brain's microenvironment during disease. [Read the Full Post]

Nuclear-Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

433 views | Feb 28 2020

Dongqing Yan et al. implicated NCT as a potential therapeutic target in myelofibrosis and provide a rationale for clinical evaluation in ruxolitinib-exposed patients with myelofibrosis. [Read the Full Post]

An in vitro assay for biomarker discovery and dose prediction applied to ibrutinib plus venetoclax treatment of CLL

279 views | Feb 27 2020

Eide CA et al. suggested that IBR + VEN may represent an effective therapeutic option for patients with AML. [Read the Full Post]

Venetoclax, a BCL-2 Inhibitor, Enhances the Efficacy of Chemotherapeutic Agents in Wild-Type ABCG2-Overexpression-Mediated MDR Cancer Cells

336 views | Feb 27 2020

Wang JQ et al. provided useful guidance in combination therapy against wild-type ABCG2-mediated MDR cancer in clinical practice. [Read the Full Post]