Cancers, Vol. 11, Pages 1604: The Brain Penetrating and Dual TORC1/TORC2 Inhibitor, RES529, Elicits Anti-Glioma Activity and Enhances the Therapeutic Effects of Anti-Angiogenetic Compounds in Preclinical Murine Models

Conclusions. In summary, RES529, the first dual TORC1/TORC2 dissociative inhibitor, lacking affinity for ABCB1/ABCG2 and having good brain penetration, was active in GBM preclinical/murine models giving credence to its use in clinical trial for patients with GBM treated in association with anti-angiogenetic compounds.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

Related Links:

CONCLUSIONS: GDC-0084 demonstrated classic PI3K/mTOR-inhibitor related toxicities. FDG-PET and concentration data from brain tumor tissue suggest that GDC-0084 crossed the blood-brain barrier. PMID: 31937616 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Abstract PURPOSE: Pediatric low-grade glioma (pLGG) is the most prevalent childhood brain tumor. Patients with BRAF V600 mutation-positive pLGG may benefit from treatment with dabrafenib. Part 2 of a phase I/IIa study, open-label study (NCT01677741) explores the activity and safety of dabrafenib treatment in these patients. PATIENTS AND METHODS: Patients ages 1 to
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Park Chung Kang Despite the presence of aggressive treatment strategies, glioblastoma remains intractable, warranting a novel therapeutic modality. An oral antipsychotic agent, penflurido (PFD), used for schizophrenia treatment, has shown an antitumor effect on various types of cancer cells. As glioma sphere-forming cells (GSCs) are known to mediate drug resistance in glioblastoma, and considering that antipsychotics can easily penetrate the blood-brain barrier, we investigated the antitumor effect of PFD on patient-derived GSCs. Using five GSCs, we found that PFD exerts an antiproliferative effect in a time- an...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
miR‑378a‑3p inhibits cellular proliferation and migration in glioblastoma multiforme by targeting tetraspanin 17. Oncol Rep. 2019 Aug 20;: Authors: Guo XB, Zhang XC, Chen P, Ma LM, Shen ZQ Abstract Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor and patients with this disease tend to have poor clinical outcome. MicroRNAs (miRs) are important regulators of a number of key pathways implicated in tumor pathogenesis. Recently, the expression of miR‑378 was shown to be dysregulated in several different types of cancer, including gastric cancer, colorectal cancer and oral ca...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
ConclusionsThe CNS penetration observed was encouraging enough to move ribociclib forward with preclinical efficacy studies in models of pediatric brain tumors.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
Alla S. Koltsova1,2, Anna A. Pendina1, Olga A. Efimova1*, Olga G. Chiryaeva1, Tatyana V. Kuznetzova1 and Vladislav S. Baranov1,2 1D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia 2Department of Genetics and Biotechnology, Saint Petersburg State University, Saint Petersburg, Russia In the present review, we focus on the phenomenon of chromothripsis, a new type of complex chromosomal rearrangements. We discuss the challenges of chromothripsis detection and its distinction from other chromoanagenesis events. Along with already known causes and mechanisms, we introdu...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
In this study, to improve our understanding of the role of ATP1A1 in the malignant phenotype and pathogenesis of GSCs, we evaluated ATP1A1 expression in GBMs of different grades and in two primary GSC lines established from human GBM tissues. We evaluated the role of ATP1A1 in GSC growth, its interactions with Src, and the activation of the ERK1/2 and AKT pathways. Our results revealed that ATP1A1 acts as an oncogene in our GSC models and targeting ATP1A1/Src may suppress GSC proliferation and growth. Materials and Methods Cell Isolation and Culture Human brain GBM tissues were from pathologically confirmed surgical spe...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion Most head and neck pathologies show a broad cellular heterogeneity making it difficult to achieve an accurate diagnosis and efficient treatment (Graf and Zavodszky, 2017; Lo Nigro et al., 2017). Single cell analysis of circadian omics (Lande-Diner et al., 2015; Abraham et al., 2018), may be a crucial tool needed in the future to fully understand the circadian control of head and neck diseases. It becomes more obvious that there is only a small genetic component but a largely unknown epigenetics and/or environmental component for most of the head and neck pathologies (Moosavi and Motevalizadeh Ardekani, 2016; He...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroinfla...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
More News: Avastin | Brain | Brain Cancers | Brain Tumor | Cancer | Cancer & Oncology | Chemotherapy | Clinical Trials | Glioma | Neurology | Oral Cancer