Blog of Signaling Pathways

Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations

150 views | May 15 2019

Greger JG et al. showed that NRAS and/or MEK mutations contribute to BRAF inhibitor resistance in vitro, and the combination of GSK2118436 and GSK1120212 overcomes this resistance. [Read the Full Post]

Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success

176 views | May 14 2019

Cazzaniga ME et al. proposed a series of practical recommendations for multidisciplinary clinical management of the various toxicities associated with the addition of targeted agents to endocrine therapy. [Read the Full Post]

Effects of Epacadostat on Brain Extracellular Fluid Concentrations of Serotonin -- An Intracerebral Microdialysis Study in Sprague-Dawley Rats

323 views | May 14 2019

Zhang Y et al. suggested that serotonin syndrome is unlikely following treatment with either epacadostat alone or with combination with MAOIs such as linezolid. [Read the Full Post]

Molecular detection of Hsp90 inhibitor suppressing PCV2 replication in host cells

316 views | May 13 2019

Liu J et al. highlighted the importance of cellular proteins during PCV2 infection and the possibility of targeting cellular chaperones for developing new anti-rotaviral strategies. [Read the Full Post]

Dependency of Cholangiocarcinoma on Cyclin D-Dependent Kinase Activity

194 views | May 13 2019

Sittithumcharee G et al. proposed that the CDK4/6-pRB pathway is a suitable therapeutic target for CCA treatment. This article is protected by copyright. All rights reserved. [Read the Full Post]

Update Breast Cancer 2019 Part 2 - Implementation of Novel Diagnostics and Therapeutics in Advanced Breast Cancer Patients in Clinical Practice

212 views | May 10 2019

This review summarises the latest studies and publications and evaluates them in regard to the relevance for clinical practice. [Read the Full Post]

The Chk1 inhibitor MK-8776 increases the radiosensitivity of human triple-negative breast cancer by inhibiting autophagy

251 views | May 09 2019

Zhou ZR et al. suggested that MK-8776increases human TNBC radiosensitivity by inhibiting irradiation-induced autophagy and that MK-8776 may be a potential agent in the radiosensitization of human TNBC. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

371 views | May 09 2019

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]

Puromycin based inhibitors of aminopeptidases for the potential treatment of hematologic malignancies

184 views | May 08 2019

Singh R et al. indicated that effective inhibitors of Puromycin-Sensitive Aminopeptidase (PSA) are di sclosed here. These potential therapeutic agents display superior in vitro antitumor potency against two leukemic cell lines, as compared to known inhibitors of aminopeptidases. [Read the Full Post]

Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial

275 views | May 08 2019

Sax PE et al. indicated at 48 weeks, virological suppression with the bictegravir regimen was achieved and was non-inferior to the dolutegravir regimen in previously untreated adults. There was no emergent resistance to either regimen. The fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide was safe and well tolerated compared with the dolutegravir regimen. [Read the Full Post]

Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial

419 views | May 07 2019

Shaw AT et al. indicated lorlatinib might be an effective therapeutic strategy for patients with ALK-positive NSCLC who have become resistant to currently available TKIs, including second-generation ALK TKIs, and is being investigated in a phase 3 randomised controlled trial comparing lorlatinib to crizotinib (, NCT03052608). [Read the Full Post]

Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo

339 views | May 07 2019

Helfrich BA et al. suggested that SCLC tumors with cMYC amplification/high gene expression will frequently respond to Aurora B inhibitors and that clinical studies coupled with predictive biomarkers are indicated. [Read the Full Post]

Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling

429 views | May 06 2019

Kuusanmäki H et al. showed alternative approaches to inhibit STAT3 activity and suggest Hsp90 as a therapeutic target in lymphoproliferative disorders with constitutively active STAT3. [Read the Full Post]

MPP+ induces necrostatin-1- and ferrostatin-1-sensitive necrotic death of neuronal SH-SY5Y cells

0 views | May 06 2019

Ito K et al. found that MPP+ predominantly induced non-apoptotic death of neuronally differentiated SH-SY5Y cells. This cell death was strongly inhibited by necrostatin-1 (Nec-1), a necroptosis inhibitor, and by an indole-containing compound (3,3'-diindolylmethane: DIM). However, it occurred independently of receptor-interacting serine/threonine-protein kinase 1/3 (RIP1/RIP3), indicating that this form of cell death was not necroptosis. MPP+-induced cell death was also inhibited by several inhibitors of ferroptosis, including ferrostatin-1 (Fer-1). Although MPP+-induced death and ferroptosis shared some features, such as occurrence of lipid peroxidation and inhibition by Fer-1, MPP+-induced death seemed to be distinct from ferroptosis because MPP+-induced death (but not ferroptosis) was inhibited by Nec-1, was independent of p53, and was accompanied by ATP depletion and mitochondrial swelling. Further investigation of MPP+-induced non-apoptotic cell death may be useful for understanding the mechanisms of neuronal loss and for treatment of neurodegenerative diseases such as Parkinson's disease. [Read the Full Post]

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models

0 views | May 04 2019

Lehmann C et al. provided functional and molecular insight on the superior anti-tumor activity of combined idasanutlin and venetoclax treatment in AML and support its further exploration in clinical studies. [Read the Full Post]

Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties

408 views | May 04 2019

Lawrence CP et al. demonstrated that both z-VAD-FMK and z-IETD-FMK are immunosuppressive in vitro and inhibit T cell proliferation without blocking the processing of caspase-8 and caspase-3. [Read the Full Post]

Simultaneous long-lasting regression of multiple nevi and melanoma metastases after ipilimumab therapy

199 views | May 03 2019

Plaquevent M et al. suggested that a major regression of multiple nevi on ipilimumab might be associated with immunotherapy response. [Read the Full Post]

Embryonic stem cells differentiated into neuron-like cells using SB431542 small molecule on nanofibrous PLA/CS/Wax scaffold

267 views | May 03 2019

Hoveizi E et al. revealed that electrospun PLA/CS/Wax scaffolds associated with the induction medium can assemble proper conditions for stem cell differentiation into NLCs. [Read the Full Post]

Vemurafenib Treatment of Pleomorphic Xanthoastrocytoma in a Child With Down Syndrome

190 views | May 02 2019

Petruzzellis G et al. report the case of an 8-years-old child with DS that presented to our attention for neurological and endocrinological issues. [Read the Full Post]

Mortalin (GRP75/HSPA9) Promotes Survival and Proliferation of Thyroid Carcinoma Cells

154 views | May 02 2019

Mito-CP-induced cell death was partially rescued by mortalin overexpression, suggesting that Mito-CP may inactivate a mechanism that requires mortalin function. These findings support the significance of mortalin and mitochondrial activity in a broad spectrum of thyroid cancer. [Read the Full Post]