Blog of Signaling Pathways

Targeted blockade of HSP90 impairs DNA-damage response proteins and increases the sensitivity of ovarian carcinoma cells to PARP inhibition

509 views | May 19 2019

Gabbasov R et al. suggested that HSP90 inhibition has the potential to sensitize some HGSOC patients without HR pathway alterations to PARPi, and potentially other DNA-damage inducing agents. [Read the Full Post]

Clinical efficacy of daratumumab, pomalidomide, and dexamethasone in patients with relapsed or refractory myeloma: Utility of re-treatment with daratumumab among refractory patients

232 views | May 19 2019

Nooka AK et al. highlighted the fact that the introduction of monoclonal antibody combination strategies and IMiDs as earlier lines of therapeutic options potentially could deliver better clinical outcomes. [Read the Full Post]

Low-intensity pulsed ultrasound promotes the proliferation of human bone mesenchymal stem cells by activating PI3K/AKt signaling pathways

595 views | May 18 2019

Xie S et al. suggested that LIPUS exposure may be involved in the proliferation of hBMSCs via activation of the PI3K/AKt signaling pathway and high expression of cyclin D1, and the intensity of 50 or 60 mW/cm2 and exposure time of 5 minutes were determined to be the optimal parameters for LIPUS exposure. [Read the Full Post]

Hydroxysafflor yellow A inhibited lipopolysaccharide-induced non-small cell lung cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT/mTOR and ERK/MAPK signaling pathways

440 views | May 18 2019

HYSA suppressed LPS-mediated proliferation, migration, invasion, and EMT in A549 and H1299 cells by inhibiting the PI3K/Akt/mTOR and ERK/MAPK signaling pathways, indicating that HYSA may be a potential candidate to treat inflammation-mediated NSCLC. [Read the Full Post]

Inhibition of apoptosis by caspase inhibitor Z-VAD-FMK improves cryotolerance of in vitro derived bovine embryos

985 views | May 17 2019

Pero ME et al. found that the addition of 20 μM Z-VAD-FMK during vitrification/warming and post-warming culture partially inhibits cryopreservation-induced apoptosis by reducing the level of active caspase 3, suggesting a potential use 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]

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.

574 views | May 17 2019

Herbertz S et al. summarized the past and current experiences with different pharmacological treatments that enabled galunisertib to be investigated in patients. [Read the Full Post]

First-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma

539 views | May 16 2019

On the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation. [Read the Full Post]

Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study

343 views | May 16 2019

Long GV et al. demonstrated that durable (≥3 years) survival is achievable with dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting. [Read the Full Post]

Effects of EF-24, RAD001, and paclitaxel on the expression profiles of apoptotic and anti-apoptotic genes

944 views | May 15 2019

Alp E et al. showed that response of these cells to paclitaxel, EF-24, and RAD001 was found different at the transcriptional level of apoptotic and antiapoptotic genes. [Read the Full Post]

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

351 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

396 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

693 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

639 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

429 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

414 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

467 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

894 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

448 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

573 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

812 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 (ClinicalTrials.gov, NCT03052608). [Read the Full Post]