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Expert Opinion on Therapeutic Targets

Luigi Fattore, Rita Mancini, Paolo Antonio Ascierto, Gennaro Ciliberto
Introduction The advent of targeted therapies and immunecheckpoints inhibitors has enhanced the treatment of metastatic melanomas. Despite striking improvements of patients' survival, drug resistance continues to limit the efficacy of such treatments. Genetic and non genetic/adaptive mechanisms of resistance could be involved; in the latter mechanism, non coding RNAs (ncRNAs) are emerging as key players. Areas covered This article outlines the current knowledge of ncRNA involvement in BRAF-mutant melanomas and the development of resistance to targeted/immuno-therapies...
December 3, 2018: Expert Opinion on Therapeutic Targets
Asheebo Rojas, Di Chen, Thota Ganesh, Nicholas H Varvel, Raymond Dingledine
Introduction:A robust neuroinflammatory response is a prevalent feature of multiple neurological disorders, including epilepsy and acute status epilepticus. One component of this neuroinflammatory reaction is the induction of cyclooxygenase-2 (COX-2), synthesis of several prostaglandins and endocannabinoid metabolites, and subsequent activation of prostaglandin and related receptors. Neuroinflammation mediated by COX-2 and its downstream effectors has received considerable attention as a potential target class to ameliorate the deleterious consequences of neurological injury...
November 28, 2018: Expert Opinion on Therapeutic Targets
Vishwaraj Sontake, Prathibha R Gajjala, Rajesh K Kasam, Satish K Madala
Fibrosis is an irreversible pathological endpoint in many chronic diseases, including pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal condition characterized by (myo)fibroblast proliferation and transformation in the lung, expansion of the extracellular matrix, and extensive remodeling of the lung parenchyma. Recent evidence indicates that IPF prevalence and mortality rates are growing in the United States and elsewhere. Despite decades of research on the pathogenic mechanisms of pulmonary fibrosis, few therapeutics have succeeded in the clinic, and they have failed to improve IPF patient survival...
November 23, 2018: Expert Opinion on Therapeutic Targets
Tarek K Rajji
In 2017, it was estimated that close to 50 million people were living with dementia worldwide and this number is expected to double every 20 years. No effective treatment exists yet probably because by the time Alzheimer's dementia (AD) has developed it is too late to intervene. Areas covered: Mild cognitive impairment (MCI) is a clinical state that typically precedes AD. In MCI, the prefrontal cortex supports compensatory mechanisms that depend on robust synaptic plasticity and that delay progression to AD...
November 19, 2018: Expert Opinion on Therapeutic Targets
Fanni A Boros, Péter Klivényi, József Toldi, László Vécsei
Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder. Despite the severe motor, psychiatric and cognitive symptoms and the great socioeconomic burden caused by the disease, available treatment is mainly symptomatic. The kynurenine pathway (KP) is the main metabolic route of tryptophan degradation, in the course of which several neuroactive compounds are generated. The imbalance of the neurotoxic and neuroprotectant metabolites can lead to excitotoxicity and overproduction of reactive oxygen species, which both contribute to the progression of HD...
November 19, 2018: Expert Opinion on Therapeutic Targets
Shaogen Wu, Jamie Bono, Yuan-Xiang Tao
Current treatments for neuropathic pain are limited at least in part due to the incomplete understanding of its underlying mechanisms. Recent evidence reveals the dysregulated expression of long non-coding RNAs (lncRNAs) in the damaged nerve, dorsal root ganglion (DRG), and spinal cord dorsal horn following peripheral nerve injury. However, the role of the majority of lncRNAs in neuropathic pain genesis is still elusive. Unveiling the mechanisms of how lncRNAs participate in neuropathic pain may develop new strategies to prevent and/or treat this disorder...
November 18, 2018: Expert Opinion on Therapeutic Targets
Innocenzo Rainero, Alessandro Vacca, Fausto Roveda, Flora Govone, Annalisa Gai, Elisa Rubino
Migraine is a common neurovascular disorder classified by the World Health Organization as one of the most debilitating diseases. Migraine is a complex disease and is a consequence of an interaction between genetic, epigenetic and environmental factors. The MTHFR gene is one of the few replicated genetic risk factors for migraine and encodes an enzyme that is crucial for the folate and the methionine cycles. Individuals carrying the T allele of the MTHFR C677T polymorphism have increased plasma concentrations of homocysteine which leads to endothelial cell injury and alterations in coagulant properties of blood...
November 17, 2018: Expert Opinion on Therapeutic Targets
Jolien Roovers, Peter De Jonghe, Sarah Weckhuysen
Gene regulation is the term used to describe the mechanisms by which a cell increases or decreases the amount of a gene product (RNA or protein). In complex organs such as the brain, gene regulation is of the utmost importance; aberrations in the regulation of specific genes can lead to neurological disorders. Understanding these mechanisms can create new strategies for targeting these disorders and progress is being made. Two drugs that function at the RNA level (nusinersen and eteplirsen) have now been approved by the FDA for the treatment of Spinomuscular atrophy and Duchenne muscular dystrophy, respectively; several other compounds for neurological disease are currently being investigated in preclinical studies and clinical trials...
October 29, 2018: Expert Opinion on Therapeutic Targets
Laura Hüser, Daniel Novak, Viktor Umansky, Peter Altevogt, Jochen Utikal
SOX2 is a transcription factor that is important in the development and maintenance of the stem cell state. Furthermore, SOX2 is associated with cancer progression because it promotes the migration, invasion, and proliferation of cancer cells. SOX2 is also expressed in cancer stem cells and appears to be involved in the resistance toward anticancer therapies. These features render SOX2 an attractive target for cancer therapy. Areas covered: In this review, we highlight the role of SOX2 in cancer and in the resistance toward anticancer therapies...
October 26, 2018: Expert Opinion on Therapeutic Targets
Johannes Foßelteder, George A Calin, Martin Pichler
No abstract text is available yet for this article.
October 26, 2018: Expert Opinion on Therapeutic Targets
Robert Prior, Lawrence Van Helleputte, Yvonne Eileen Klingl, Ludo Van Den Bosch
Peripheral neuropathies are a heterogeneous group of diseases that are characterized by a progressive, ascending loss of nerve function arising from the peripheral regions of the limbs. The phenotypic overlap between different types of hereditary and acquired peripheral neuropathies indicates that similar pathophysiological processes are at play. Many downstream pathways in peripheral neurons, such as axonal transport, protein degradation and interactions with Schwann cells, organelle damage, channelopathies and neuroinflammatory signalling, have been proposed; each affects peripheral nerves in a negative way...
October 25, 2018: Expert Opinion on Therapeutic Targets
Éva Leiter, László Csernoch, István Pócsi
Diseases caused by pathogenic fungi are increasing because of antibiotic overuse, the rise of immunosuppressive therapies, and climate change. The limited variety of antimycotics and the rapid adaptation of pathogenic fungi to antifungal agents serve to exacerbate this issue. Unfortunately, about 1.6 million people are killed by fungal infections annually. Areas covered: The discovery of the small antimicrobial proteins produced by microorganisms, animals, humans, and plants will hopefully overcome challenges in the treatment of fungal infections...
October 25, 2018: Expert Opinion on Therapeutic Targets
Yoon Jin Cha, Ja Seung Koo
Adipocytes, which represent a substantial part of the tumor microenvironment in breast cancer, secrete several adipokines that affect tumorigenesis, cancer progression, metastasis, and treatment resistance via multiple signaling pathways. Areas covered: In this review, we focus on the role of leptin, adiponectin, autotaxin, and interleukin-6 in breast cancer initiation, progression, metastasis, and drug response. Furthermore, we investigated adipokines as potential targets of breast cancer-specific drugs. Expert opinion: Adipokines and adipokine receptors are deregulated in breast cancer...
October 24, 2018: Expert Opinion on Therapeutic Targets
Liang Wang, Imad Shureiqi, John R Stroehlein, Daoyan Wei
No abstract text is available yet for this article.
October 24, 2018: Expert Opinion on Therapeutic Targets
Daniela Magliulo, Rosa Bernardi
Hypoxia-inducible transcription factors have been identified as regulators of adaptive responses to hypoxia. Over the past 20 years, more than 8000 papers have described their increasingly complex role and regulation in cancer. Presently, it is recognized that hypoxia-inducible factors (HIFs) are regulated by oxygen-dependent and oxygen-independent mechanisms in cancer development; the list of their targets has increased to include more than 500 genes involved in most hallmarks of cancer. Areas covered: Most literature describes the function of HIF factors in solid tumors; however, in the past 10 years, evidence has steadily accumulated to indicate that HIFs are implicated in hematological malignancies...
October 20, 2018: Expert Opinion on Therapeutic Targets
Kelly Van Looveren, Claude Libert
Reverting Systemic inflammatory response syndromes (SIRS), particularly sepsis, is a huge challenge of contemporary medicine. Inhibition of the cytokine tumor necrosis factor alpha (TNFα), originally considered as a mediator in sepsis, has led to frustrating results. Equally so, glucocorticoids (GCs), renowned for their role in numerous inflammatory diseases, remain controversial in sepsis. Areas covered: We discuss how, in SIRS, the intestinal epithelium is a critical TNF-responsive target. Inhibition of TNF receptor 1 (TNFR1), rather than TNF, may be a more targeted and safe therapeutic approach...
October 20, 2018: Expert Opinion on Therapeutic Targets
Maud-Emmanuelle Gilles, Frank J Slack
MicroRNAs (miRNA) are a class of small non-coding RNA that play a major role in various cellular processes by negatively regulating gene expression. In the past decade, miRNA dysregulation has been reported to be closely linked to inflammatory diseases. The immune response modulates cancer initiation and progression; miRNAs including let-7 family members have been shown to act as key regulators of the immune responses in various diseases and cancers. Notably, the let-7 miRNA has been reported to be closely associated with immunity, specifically with Toll-like receptors that mediate cytokine expression during pathogen infection and with the regulation of various other immune effectors...
October 17, 2018: Expert Opinion on Therapeutic Targets
David B Sykes
No abstract text is available yet for this article.
October 13, 2018: Expert Opinion on Therapeutic Targets
Timo Uphaus, Frauke Zipp, Catherine Larochelle
No abstract text is available yet for this article.
October 12, 2018: Expert Opinion on Therapeutic Targets
F David Carmona, Javier Martín Ibáñez
PTPN22 encodes a lymphoid-specific tyrosine phosphatase (LYP) that is a master regulator of the immune response. This gene is a major susceptibility factor for a wide range of autoimmune conditions, including rheumatoid arthritis (RA) for which it represents the strongest non-HLA contributor to disease risk. A missense PTPN22 allele (R620W) affecting the protein-protein interaction of LYP with other relevant players was described as the functional variant of the association. This review will focus on the role of PTPN22 in the pathogenic mechanisms underlying RA predisposition and discuss the possibility of developing LYP-based treatment strategies with a potential application in clinical practice...
September 25, 2018: Expert Opinion on Therapeutic Targets
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