ATF4-amino acid circuits: a recipe for resistance in melanoma

Lactate dehydrogenase A (LDHA) has appropriately received attention as a therapeutic target for the treatment of a broad spectrum of tumor types, yet little is known regarding intrinsic resistance to LDHA inhibitors. Pathria et al (2018) now establish that ATF4-dependent control of enzymes that direct amino acid metabolism confers resistance to LDHA inhibitors in melanoma and identify chokepoints that can be exploited to overcome metabolic compensation, setting the stage for trials with such combinations.
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Cancer, Metabolism News [amp ] Views Source Type: research

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Conditions:   Melanoma;   Non-Small Cell Lung Cancer Intervention:   Drug: Single Arm Sponsors:   Cytosite Biopharma Inc.;   Massachusetts General Hospital;   University of Alabama at Birmingham Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Abstract The complexity of the immune response and diversity of targets challenges conventional conceptual frameworks used in selecting and monitoring treatment with immune check-point inhibitors. The limitations of anatomic imaging in assessing response have been recognized. Varying patterns of response have been recognized. These patterns have different implications for the continuation and duration of therapy. Evidence supporting the role of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography as a prognostic biomarker and in characterizing response is presented. An added benefit of this appr...
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Tags: PET Clin Source Type: research
The impact of intratumoral heterogeneity (ITH) and the resultant neoantigen landscape on T cell immunity are poorly understood. ITH is a widely recognized feature of solid tumors and poses distinct challenges related to the development of effective therapeutic strategies, including cancer neoantigen vaccines. Here, we performed deep targeted DNA sequencing...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: PNAS Plus Source Type: research
-Hui Lee Nan-Shan Chang Membrane hyaluronidase Hyal-2 supports cancer cell growth. Inhibition of Hyal-2 by specific antibody against Hyal-2 or pY216-Hyal-2 leads to cancer growth suppression and prevention in vivo. By immunoelectron microscopy, tumor suppressor WWOX is shown to be anchored, in part, in the cell membrane by Hyal-2. Alternatively, WWOX undergoes self-polymerization and localizes in the cell membrane. Proapoptotic pY33-WWOX binds Hyal-2, and TGF-β induces internalization of the pY33-WWOX/Hyal-2 complex to the nucleus for causing cell death. In contrast, when pY33 is downregulated and pS14 upreg...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
(Sanford Burnham Prebys Medical Discovery Institute) Scientists at Sanford Burnham Prebys Medical Discovery Institute have identified a combination of two anti-cancer compounds that shrank pancreatic tumors in mice -- supporting the immediate evaluation of the drugs in a clinical trial. US Food and Drug Administration (FDA)-approved versions of the compounds are used today to treat certain leukemias and solid tumors, including melanoma. The study was published in Nature Cell Biology.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Cancers, Vol. 11, Pages 1806: Complex Formation with Monomeric α-Tubulin and Importin 13 Fosters c-Jun Protein Stability and Is Required for c-Jun’s Nuclear Translocation and Activity Cancers doi: 10.3390/cancers11111806 Authors: Melanie Kappelmann-Fenzl Silke Kuphal Rosemarie Krupar Dirk Schadendorf Viktor Umansky Lily Vardimon Claus Hellerbrand Anja-Katrin Bosserhoff Microtubules are highly dynamic structures, which consist of α- and β-tubulin heterodimers. They are essential for a number of cellular processes, including intracellular trafficking and mitosis. Tubulin-b...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
This article is one of a series discussing cancer prevention and detection in primary care. Here we focus on the most common types of skin cancer: melanoma, squamous cell carcinoma and basal cell carcinoma. We describe the main risk factors and prevention advice. We summarise key guidance on the sy mptoms and signs of skin cancers and their management, including their initial assessment and referral. In addition, we review emerging technologies and diagnostic aids which may become available for use in primary care in the near future, to aid the triage of suspicious skin lesions.
Source: Advances in Therapy - Category: Drugs & Pharmacology Source Type: research
AbstractCircularRNAs (circRNAs) are non-coding RNAs which compete for microRNA (miRNA) binding, influencing the abundance and stability of other RNA species. Herein we have investigated the effect of circRNAs on the mir200-ZEB1 feedback loop in relationship with the aggressiveness of human melanoma cells. We first compared the level of expression of key factors in the mir200-ZEB1 feedback loop in primary human melanoma cells compared with their matching metastatic one and found a correlation between the aggressiveness of the cells and the level of expression of ZEB1 and SNAI1. We also analyzed factors in the mir200-ZEB1 fe...
Source: Cancer Microenvironment - Category: Cancer & Oncology Source Type: research
This study documents that the loss of BAP1 nuclear expression is quite a frequent finding in PCC/PGL, suggesting a possible role ofBAP1 in the pathogenesis of these tumors. Gene mutations do not seem to be involved in this loss of expression, at least in most cases. Other genetic and epigenetic mechanisms need to be further investigated.
Source: Endocrine Pathology - Category: Pathology Source Type: research
Conditions:   Skin Cancer, Non-Melanoma;   Skin Cancer Melanoma;   Mohs Micrographic Surgery Intervention:   Sponsors:   University of Pennsylvania;   Oregon Health and Science University;   Stanford University;   University of Minnesota;   University of Missouri-Columbia;   University of Vermont;   University of Nebraska Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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