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Expert Opinion on Therapeutic Targets

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https://www.readbyqxmd.com/read/29235382/exploiting-differential-rna-splicing-patterns-a-potential-new-group-of-therapeutic-targets-in-cancer
#1
Nidhi Jyotsana, Michael Heuser
Mutations in genes associated with splicing have been found in hematologic malignancies, but also in solid cancers. Aberrant cancer specific RNA splicing either results from mutations or misexpression of the spliceosome genes directly, or from mutations in splice sites of oncogenes or tumor suppressors. Areas covered: In this review, we present molecular targets of aberrant splicing in various malignancies, information on existing and emerging therapeutics against such targets, and strategies for future drug development...
December 13, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29207896/rho-gtpase-effectors-and-nad-metabolism-in-cancer-immune-suppression
#2
Mahmoud Chaker, Audrey Minden, Suzie Chen, Robert H Weiss, Eduardo N Chini, Amit Mahipal, Asfar S Azmi
Sustained proliferative signaling and de-regulated cellular bioenergetics are two of the chief hallmarks of cancer. Alterations in the Ras pathway and its downstream effectors are among the major drivers for uncontrolled cell growth in many cancers. The GTPases are one of the signaling molecules that activate crucial signal transducing pathways downstream of Ras through several effector proteins. The GTPases (GTP bound) interact with several effectors and modulate a number of different biological pathways including those that regulate cytoskeleton, cellular motility, cytokinesis, proliferation, apoptosis, transcription and nuclear signaling...
December 6, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29171762/plk4-a-link-between-centriole-biogenesis-and-cancer
#3
Radhika Radha Maniswami, Seema Prashanth, Archana Venkataramana Karanth, Sindhu Koushik, Hemalatha Govindaraj, Ramesh Mullangi, Sriram Rajagopal, Sooriya Kumar Jegatheesan
Polo like kinase (PLK) is known to play a pivotal role in various cell cycle processes to perpetuate proper division and growth of the cells. Polo like kinase-4 (PLK4) is one such kinase that appears in low abundance and plays a well-characterized role in centriole duplication. PLK4 deregulation (i.e. both overexpression and depletion of PLK4), leads to altered mitotic fidelity and thereby triggers tumorigenesis. Hence, over the last few years PLK4 has emerged as a potential therapeutic target for the treatment of various advanced cancers...
November 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29168935/epithelial-plasticity-and-metastatic-cascade
#4
Minal Garg
No abstract text is available yet for this article.
November 23, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29168929/kinin-b1-receptors-as-a-therapeutic-target-for-inflammation
#5
Fatimunnisa Qadri, Michael Bader
Kinins are peptide mediators exerting their pro-inflammatory actions by the selective stimulation of two distinct G-protein coupled receptors, termed BKB1R and BKB2R. While BKB2R is constitutively expressed in a multitude of tissues, BKB1R is hardly expressed at baseline but highly inducible by inflammatory mediators. In particular, BKB1R was shown to be involved in the pathogenesis of numerous inflammatory diseases. Areas covered: This review intends to evaluate the therapeutic potential of substances interacting with the BKB1R...
November 23, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29168923/calpain-2-as-a-therapeutic-target-for-acute-neuronal-injury
#6
Yubin Wang, Xiaoning Bi, Michel Baudry
Introduction Calpains represent a family of neutral, calcium-dependent proteases, which modify the function of their target proteins by partial truncation. These proteases have been implicated in numerous cell functions, including cell division, proliferation, migration, and death. In the CNS, where calpain-1 and calpain-2 are the main calpain isoforms, their activation has been linked to synaptic plasticity as well as to neurodegeneration. This review will focus on the role of calpain-2 in acute neuronal injury and discuss the possibility of developing selective calpain-2 inhibitors for therapeutic purposes...
November 23, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29168406/tgf%C3%AE-as-a-therapeutic-target-in-cystic-fibrosis
#7
Elizabeth Kramer, John P Clancy
Cystic fibrosis (CF) is a genetic disease characterized by progressive lung disease. Most CF therapies focus on treating secondary pulmonary complications rather than addressing the underlying processes inducing airway remodeling and ineffective response to infection. Transforming growth factor beta (TGFβ) is a cytokine involved in fibrosis, inflammation, and injury response as well as a genetic modifier and biomarker of CF lung disease. Targeting the TGFβ pathway has been pursued in other diseases, but the mechanism of TGFβ effects in CF is less well understood...
November 23, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29166798/grk2-as-a-therapeutic-target-for-heart-failure
#8
Alessandro Cannavo, Klara Komici, Leonardo Bencivenga, Maria Loreta D'amico, Giuseppina Gambino, Daniela Liccardo, Nicola Ferrara, Giuseppe Rengo
G protein-coupled receptor (GPCR) kinase-2 (GRK2) is a regulator of GPCRs, in particular β-adrenergic receptors (ARs), and as demonstrated by decades of investigation, it has a pivotal role in the development and progression of cardiovascular disease, like heart failure (HF). Indeed elevated levels and activity of this kinase are able to promote the dysfunction of both cardiac and adrenal α- and β-ARs and to dysregulate other protective signaling pathway, such as sphingosine 1-phospate and insulin. Moreover, recent discoveries suggest that GRK2 can signal independently from GPCRs, in a 'non-canonical' manner, via interaction with non-GPCR molecule or via its mitochondrial localization...
November 23, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29148857/update-on-the-role-and-therapeutic-potential-of-polycomb-repressive-complexes-in-biliary-tract-cancer
#9
Daniel Neureiter, Tobias Kiesslich, Markus Ritter, Christian Mayr
No abstract text is available yet for this article.
November 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29148850/atad2-in-cancer-a-pharmacologically-challenging-but-tractable-target
#10
Muzammal Hussain, Yang Zhou, Yu Song, H M Adnan Hameed, Hao Jiang, Yaoquan Tu, Jiancun Zhang
ATAD2 protein is an emerging oncogene that has strongly been linked to the etiology of multiple advanced human cancers. Therapeutically, despite the fact that genetic suppression/knockdown studies have validated it as a compelling drug target for future therapeutic development, recent druggability assessment data suggest that direct targeting of ATAD2's bromodomain (BRD) may be a very challenging task. ATAD2's BRD has been predicted as a "difficult to drug" or "least druggable" target due to the concern that its binding pocket, and the areas around it, seem to be unfeasible for ligand binding...
November 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29148847/emerging-therapeutic-targets-in-myeloproliferative-neoplasms-and-peripheral-t-cell-leukemia-and-lymphomas
#11
Anna Orlova, Bettina Wingelhofer, Heidi A Neubauer, Barbara Maurer, Angelika Berger-Becvar, György Miklós Keserű, Patrick T Gunning, Peter Valent, Richard Moriggl
Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations of chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages...
November 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29076792/targeting-il-33-st2-signaling-regulation-of-immune-function-and-analgesia
#12
Victor Fattori, Miriam S N Hohmann, Ana C Rossaneis, Marilia F Manchope, Jose C Alves-Filho, Thiago M Cunha, Fernando Q Cunha, Waldiceu A Verri
IL-33 signals through ST2 receptor and promotes inflammation by activating downstream pathways culminating in the production of pro-inflammatory mediators such as IL-1β, TNF-α, and IL-6 in an NF-κB-dependent manner. In fact, compelling evidence has demonstrated the importance of IL-33/ST2 in both innate and adaptive immune responses in diseases presenting pain as an important clinical symptom. Areas covered: IL-33 is a pleiotropic cytokine with varied immune functions. Dysregulation of this pathway has been described as a key step in varied immune responses...
November 5, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29096557/nod2-and-bacterial-recognition-as-therapeutic-targets-for-crohn-s-disease
#13
Magali de Bruyn, Séverine Vermeire
Crohn's disease (CD) is a chronic, disabling disease of the gastrointestinal tract that mostly affects young adults. Despite extensive research, the pathogenesis of CD is still not completely understood. It is thought that an abnormal mucosal immune response is elicited towards the luminal microbiota in genetically predisposed persons. Genome-wide association studies and meta-analysis have greatly improved our insight into the genetic background of CD. One of the most studied CD-associated genes is nucleotide-binding oligomerization domain 2 (NOD2)...
November 2, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29063813/the-eif2-alpha-kinase-hri-a-potential-target-beyond-the-red-blood-cell
#14
Nicholas Burwick, Bertal H Aktas
The eIF2α kinase heme-regulated inhibitor (HRI) is one of four well-described kinases that phosphorylate eIF2α in response to various cell stressors, resulting in reduced ternary complex formation and attenuation of mRNA translation. Although HRI is well known for its role as a heme sensor in erythroid progenitors, pharmacologic activation of HRI has been demonstrated to have anti-cancer activity across a wide range of tumor sub-types. Here, the potential of HRI activators as novel cancer therapeutics is explored...
October 30, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29076382/emerging-therapeutic-targets-currently-under-investigation-for-the-treatment-of-systemic-amyloidosis
#15
Mario Nuvolone, Giampaolo Merlini
Systemic amyloidosis occurs when one of a growing list of circulating proteins acquires an abnormal fold, aggregates and gives rise to extracellular amyloid deposits in different body sites, leading to organ dysfunction and eventually death. Current approaches are mainly aimed at lowering the supply of the amyloidogenic precursor or at stabilizing it in a non-amyloidogenic state, thus interfering with the initial phases of amyloid formation and toxicity. Areas covered: Improved understanding of the pathophysiology is indicating novel steps and molecules that could be therapeutically targeted...
October 27, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29022407/the-potential-of-kdm3a-as-a-therapeutic-target-in-ewing-sarcoma-and-other-cancers
#16
Paul Jedlicka
No abstract text is available yet for this article.
October 13, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29076378/kca1-1-channels-as-therapeutic-targets-for-rheumatoid-arthritis
#17
Christine Beeton
No abstract text is available yet for this article.
December 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29072508/the-aquaporin-4-water-channel-as-a-potential-drug-target-in-neurological-disorders
#18
REVIEW
Alan S Verkman, Alex J Smith, Puay-Wah Phuan, Lukmanee Tradtrantip, Marc O Anderson
Aquaporin-4 (AQP4) is a water transporting protein expressed at the plasma membrane of astrocytes throughout the central nervous system (CNS). Analysis of AQP4 knockout mice has suggested its broad involvement in brain water balance, neuroexcitation, glial scarring, neuroinflammation, and even neurodegenerative and neuropsychiatric disorders. Broad clinical utility of AQP4 modulators has been speculated. Area covered: This review covers the biology of AQP4, evidence for its roles in normal CNS function and neurological disorders, and progress in AQP4 drug discovery...
December 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29067856/challenges-for-intraventricular-hemorrhage-research-and-emerging-therapeutic-targets
#19
REVIEW
Thomas Garton, Ya Hua, Jianming Xiang, Guohua Xi, Richard F Keep
Intraventricular hemorrhage (IVH) affects both premature infants and adults. In both demographics, it has high mortality and morbidity. There is no FDA approved therapy that improves neurological outcome in either population highlighting the need for additional focus on therapeutic targets and treatments emerging from preclinical studies. Areas covered: IVH induces both initial injury linked to the physical effects of the blood (mass effect) and secondary injury linked to the brain response to the hemorrhage...
December 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29065733/hepatitis-b-core-protein-as-a-therapeutic-target
#20
Lung-Yi Mak, Danny Ka-Ho Wong, Wai-Kay Seto, Ching-Lung Lai, Man Fung Yuen
Chronic hepatitis B virus (HBV) infection is difficult to cure, due to the presence of covalently-closed-circular DNA and virus-mediated blunting of host immune response. Existing therapies with nucleos(t)ide analogue or pegylated-interferon are not sufficient to achieve a high rate of HBV surface antigen seroclearance, a more desirable treatment outcome. Novel therapeutic agents targeting alternative viral replication steps are being developed. In this review, we will discuss the hepatitis B core antigen (HBcAg) as a therapeutic target...
December 2017: Expert Opinion on Therapeutic Targets
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