Strategies for the CRISPR-Based Therapeutics
Publication date: Available online 17 December 2019Source: Trends in Pharmacological SciencesAuthor(s): Bin Li, Yuyu Niu, Weizhi Ji, Yizhou DongThe CRISPR (clustered regularly interspaced short palindromic repeats)-based genome editing technology is an emerging RNA-guided nuclease system initially identified from the microbial adaptive immune systems. In recent years, the CRISPR system has been reprogrammed to target specific regions of the eukaryotic genome and has become a powerful tool for genetic engineering. Researchers have explored many approaches to improve the genome editing activity of the CRISPR–Cas system and...
Source: Trends in Pharmacological Sciences - December 18, 2019 Category: Drugs & Pharmacology Source Type: research
Overcoming the Brain Barriers: From Immune Cells to Nanoparticles
Publication date: Available online 12 December 2019Source: Trends in Pharmacological SciencesAuthor(s): Marc Charabati, Jean-Michel Rabanel, Charles Ramassamy, Alexandre PratNanoparticulate carriers, often referred to as nanoparticles (NPs), represent an important pharmacological advance for drug protection and tissue-specific drug delivery. Accessing the central nervous system (CNS), however, is a complex process regulated by mainly three brain barriers. While some leukocyte (i.e., immune cell) subsets are equipped with the adequate molecular machinery to infiltrate the CNS in physiological and/or pathological contexts, t...
Source: Trends in Pharmacological Sciences - December 13, 2019 Category: Drugs & Pharmacology Source Type: research
Oligonucleotides to the (Gene) Rescue: FDA Approvals 2017–2019
Publication date: Available online 10 December 2019Source: Trends in Pharmacological SciencesAuthor(s): Jacqueline Rüger, Silvia Ioannou, Daniela Castanotto, Cy A. SteinFour decades have passed since oligonucleotides were first used to manipulate gene expression. There were few FDA approvals prior to 2016, mostly of drugs that eventually exhibited poor performance in the market. The aura of their younger siRNA relatives had also faded during the past 15 years. However, several FDA approvals have occurred in the past 4 years, restoring hope that a new era has dawned in oligonucleotide/siRNA clinical therapeutics. Here, we ...
Source: Trends in Pharmacological Sciences - December 12, 2019 Category: Drugs & Pharmacology Source Type: research
Preserving the CTLA-4 Checkpoint for Safer and More Effective Cancer Immunotherapy
Publication date: Available online 10 December 2019Source: Trends in Pharmacological SciencesAuthor(s): Yang Liu, Pan ZhengA major paradigm in cancer immunotherapy is the use of checkpoint inhibitors to break regulatory mechanisms that usually guard the host against autoimmune diseases. CTLA-4-targeting immunotherapy was the first example that helped establish this paradigm. However, the clinically tested anti-CTLA-4 antibodies exhibit suboptimal efficacy but high toxicity. Recent studies have demonstrated that immunotherapy-related adverse events (irAE) and the cancer immunotherapeutic effect (CITE) represent distinct and...
Source: Trends in Pharmacological Sciences - December 12, 2019 Category: Drugs & Pharmacology Source Type: research
Targeting Bacterial Genomes for Natural Product Discovery
Publication date: Available online 7 December 2019Source: Trends in Pharmacological SciencesAuthor(s): Edward Kalkreuter, Guohui Pan, Alexis J. Cepeda, Ben ShenBacterial natural products (NPs) and their analogs constitute more than half of the new small molecule drugs developed over the past few decades. Despite this success, interest in natural products from major pharmaceutical companies has decreased even as genomics has uncovered the large number of biosynthetic gene clusters (BGCs) that encode for novel natural products. To date, there is still a lack of universal strategies and enabling technologies to discover natur...
Source: Trends in Pharmacological Sciences - December 8, 2019 Category: Drugs & Pharmacology Source Type: research
Targeting Mutant KRAS for Immunogenic Cell Death Induction
Publication date: Available online 6 December 2019Source: Trends in Pharmacological SciencesAuthor(s): Lorenzo GalluzziAlthough somatic KRAS mutations are common in human tumors, no inhibitor of mutant KRAS was clinically available until recently. Canon and colleagues describe the ability of a clinically available KRASG12C inhibitor to drive immunogenic cancer cell death, thus constituting a promising combinatorial partner for immune checkpoint blockers. (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - December 7, 2019 Category: Drugs & Pharmacology Source Type: research
Editorial Board and Contents
Publication date: December 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 12Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - November 26, 2019 Category: Drugs & Pharmacology Source Type: research
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Publication date: December 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 12Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - November 26, 2019 Category: Drugs & Pharmacology Source Type: research
Inhibiting Heat Shock Factor 1 in Cancer: A Unique Therapeutic Opportunity
Publication date: Available online 11 November 2019Source: Trends in Pharmacological SciencesAuthor(s): Bushu Dong, Alex M. Jaeger, Dennis J. ThieleThe ability of cancer cells to cope with stressful conditions is critical for their survival, proliferation, and metastasis. The heat shock transcription factor 1 (HSF1) protects cells from stresses such as chemicals, radiation, and temperature. These properties of HSF1 are exploited by a broad spectrum of cancers, which exhibit high levels of nuclear, active HSF1. Functions for HSF1 in malignancy extend well beyond its central role in protein quality control. While HSF1 has be...
Source: Trends in Pharmacological Sciences - November 12, 2019 Category: Drugs & Pharmacology Source Type: research
Targeting Muscarinic Acetylcholine Receptors for the Treatment of Psychiatric and Neurological Disorders
Publication date: Available online 8 November 2019Source: Trends in Pharmacological SciencesAuthor(s): Sean P. Moran, James Maksymetz, P. Jeffrey ConnMuscarinic acetylcholine receptors (mAChR) play important roles in regulating complex behaviors such as cognition, movement, and reward, making them ideally situated as potential drug targets for the treatment of several brain disorders. Recent advances in the discovery of subtype-selective allosteric modulators for mAChRs has provided an unprecedented opportunity for highly specific modulation of signaling by individual mAChR subtypes in the brain. Recently, mAChR allosteric...
Source: Trends in Pharmacological Sciences - November 9, 2019 Category: Drugs & Pharmacology Source Type: research
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Publication date: November 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 11Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - November 8, 2019 Category: Drugs & Pharmacology Source Type: research
Editorial Board and Contents
Publication date: November 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 11Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - November 8, 2019 Category: Drugs & Pharmacology Source Type: research
A Third Shot at EGFR: New Opportunities in Cancer Therapy
Publication date: Available online 6 November 2019Source: Trends in Pharmacological SciencesAuthor(s): Salvador Guardiola, Monica Varese, Macarena Sánchez-Navarro, Ernest GiraltEpidermal growth factor receptor (EGFR) inhibitors were among the first type of targeted agents discovered in cancer and currently constitute the standard of care for a wide range of lung and colon malignancies. However, the therapeutic progress achieved with these drugs has been accompanied by the identification of an ever-increasing number of acquired resistance mechanisms that inevitably appear in nearly all patients. Increased knowledge on EGFR...
Source: Trends in Pharmacological Sciences - November 7, 2019 Category: Drugs & Pharmacology Source Type: research
Charting a TRP to Novel Therapeutic Destinations for Kidney Diseases
Publication date: Available online 5 November 2019Source: Trends in Pharmacological SciencesAuthor(s): Juan Lorenzo Pablo, Anna GrekaIon channels are critical to kidney function, and their dysregulation leads to several distinct kidney diseases. Of the diversity of ion channels in kidney cells, the transient receptor potential (TRP) superfamily of proteins plays important and varied roles in both maintaining homeostasis as well as in causing disease. Recent work showed that TRPC5 blockers could successfully protect critical components of the kidney filter both in vitro and in vivo, thus revealing TRPC5 as a tractable the...
Source: Trends in Pharmacological Sciences - November 7, 2019 Category: Drugs & Pharmacology Source Type: research
Phosphodiesterase Type 4 Inhibition in CNS Diseases
Publication date: Available online 5 November 2019Source: Trends in Pharmacological SciencesAuthor(s): Arjan Blokland, Pim Heckman, Tim Vanmierlo, Rudy Schreiber, Dean Paes, Jos PrickaertsPhosphodiesterases (PDEs) have been an interesting drug target for many diseases. Although a vast number of mainly preclinical studies demonstrates beneficial effects of PDE inhibitors for central nervous system (CNS) diseases, no drugs are currently available for CNS indications. In this review, we discuss the rationale of PDE4 inhibitors for different CNS diseases, including memory impairments, striatal disorders, multiple sclerosis (MS...
Source: Trends in Pharmacological Sciences - November 7, 2019 Category: Drugs & Pharmacology Source Type: research
