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Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy

journal
https://read.qxmd.com/read/30544036/micrornas-as-a-drug-resistance-mechanism-to-targeted-therapies-in-egfr-mutated-nsclc-current-implications-and-future-directions
#1
Alessandro Leonetti, Yehuda G Assaraf, Paraskevi D Veltsista, Btissame El Hassouni, Marcello Tiseo, Elisa Giovannetti
The introduction of EGFR-tyrosine kinase inhibitors (TKIs) has revolutionized the treatment and prognosis of non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations. However, these patients display disease progression driven by the onset of acquired mechanisms of drug resistance that limit the efficacy of EGFR-TKI to no longer than one year. Moreover, a small fraction of EGFR-mutated NSCLC patients does not benefit from this targeted treatment due to primary (i...
November 28, 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/30447411/update-on-prevalence-and-mechanisms-of-resistance-to-linezolid-tigecycline-and-daptomycin-in-enterococci-in-europe-towards-a-common-nomenclature
#2
Jennifer K Bender, Vincent Cattoir, Kristin Hegstad, Ewa Sadowy, Teresa M Coque, Henrik Westh, Anette M Hammerum, Kirsten Schaffer, Karen Burns, Stephen Murchan, Carla Novais, Ana R Freitas, Luísa Peixe, Maria Del Grosso, Annalisa Pantosti, Guido Werner
Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens. Invasive VRE infections are difficult to treat since common therapeutic options including ampicillin and glycopeptides often fail. In vitro, most VRE remain susceptible to last-resort antibiotics such as linezolid, tigecycline and daptomycin. However, neither tigecycline nor linezolid act in a bactericidal manner, and daptomycin has proven activity only at high dosages licensed for treating enterococcal endocarditis. Despite these pharmacological and therapeutic limitations, reports on resistance to these last-resort drugs in VRE, and enterococci in general, have increased in recent years...
November 2, 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/30472242/the-abar-antibiotic-resistance-islands-found-in-acinetobacter-baumannii-global-clone-1-structure-origin-and-evolution
#3
Mohammad Hamidian, Ruth M Hall
In multiply resistant Acinetobacter baumannii, complex transposons located in the chromosomal comM gene carry antibiotic and heavy metal resistance determinants. For one type, known collectively as AbaR, the ancestral form, AbaR0, entered a member of global clone 1 (GC1) in the mid 1970s and continued to evolve in situ forming many variants. In AbaR0, antibiotic and mercuric ion resistance genes are located between copies of a cadmium-zinc resistance transposon, Tn6018, and this composite transposon is in a class III transposon, Tn6019, carrying arsenate/arsenite resistance genes and five tni transposition genes...
November 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/30471641/modulating-ros-to-overcome-multidrug-resistance-in-cancer
#4
Qingbin Cui, Jing-Quan Wang, Yehuda G Assaraf, Liang Ren, Pranav Gupta, Liuya Wei, Charles R Ashby, Dong-Hua Yang, Zhe-Sheng Chen
The successful treatment of cancer has significantly improved as a result of targeted therapy and immunotherapy. However, during chemotherapy, cancer cells evolve and can acquire "multidrug resistance" (MDR), which significantly limits the efficacy of cancer treatment and impacts patient survival and quality of life. Among the approaches to reverse MDR, modulating reactive oxidative species (ROS) may represent a strategy to kill MDR cancer cells that are mechanistically diverse. ROS in cancer cells play a central role in regulating and inducing apoptosis, thereby modulating cancer cells proliferation, survival and drug resistance...
November 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/30439622/window-consortium-a-path-towards-increased-therapy-efficacy-against-glioblastoma
#5
Kulsoom U Abdul, Megan Houweling, Fredrik Svensson, Ravi S Narayan, Fleur M G Cornelissen, Asli Küçükosmanoglu, Emmanouil Metzakopian, Colin Watts, David Bailey, Tom Wurdinger, Bart A Westerman
Glioblastoma is the most common and malignant form of brain cancer, for which the standard treatment is maximal surgical resection, radiotherapy and chemotherapy. Despite these interventions, mean overall survival remains less than 15 months, during which extensive tumor infiltration throughout the brain occurs. The resulting metastasized cells in the brain are characterized by chemotherapy resistance and extensive intratumoral heterogeneity. An orthogonal approach attacking both intracellular resistance mechanisms as well as intercellular heterogeneity is necessary to halt tumor progression...
October 30, 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/30466712/precision-medicine-in-head-and-neck-cancer
#6
Orit Kaidar-Person, Ziv Gil, Salem Billan
Head and Neck cancer is among the most common cancers worldwide, with a high prevalence in south East Asia, Brazil and central Europe. Head and Neck Squamous cell carcinoma (HNSCC) is associated with elevated mutational load but lacks specific genetic mutations. Exposure to carcinogens including tobacco and alcohol are the most dominant etiologic factors of HNSCC, while Epstein-Barr (HBV) and Human Papilloma Viruses (HPV) are associated with nasopharyngeal and oropharyngeal carcinoma, respectively. Surgery including open and minimally invasive procedures is considered the standard of care for the majority of oral cavity and early larynx cancers, while radiation therapy or concurrent chemoradiation are used for the other head and neck cancers...
September 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/30466711/a-close-look-onto-structural-models-and-primary-ligands-of-metallo-%C3%AE-lactamases
#7
REVIEW
Joanna E Raczynska, Ivan G Shabalin, Wladek Minor, Alexander Wlodawer, Mariusz Jaskolski
β-Lactamases are hydrolytic enzymes capable of opening the β-lactam ring of antibiotics such as penicillin, thus endowing the bacteria that produce them with antibiotic resistance. Of particular medical concern are metallo-β-lactamases (MBLs), with an active site built around coordinated Zn cations. MBLs are pan-reactive enzymes that can break down almost all classes of β-lactams, including such last-resort antibiotics as carbapenems. They are not only broad-spectrum-reactive but are often plasmid-borne (e...
September 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/30075835/host-genetic-profiling-to-increase-drug-safety-in-colorectal-cancer-from-discovery-to-implementation
#8
Erika Cecchin, Elena De Mattia, Fabrizio Ecca, Giuseppe Toffoli
Adverse events affect the pharmacological treatment of approximately 90% of colorectal cancer (CRC) patients at any stage of the disease. Chemotherapy including fluoropyrimidines, irinotecan, and oxaliplatin is the cornerstone of the pharmacological treatment of CRC. The introduction of novel targeted agents, as anti-EGFR (i.e. cetuximab, panitumumab) and antiangiogenic (i.e. bevacizumab, ziv-aflibercept, regorafenib, and ramucirumab) molecules, into the oncologist's toolbox has led to significant improvements in the life expectancy of advanced CRC patients, but with a substantial increase in toxicity burden...
July 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/30075834/targeting-invadopodia-for-blocking-breast-cancer-metastasis
#9
Tomer Meirson, Hava Gil-Henn
Dissemination of cancer cells from the primary tumor and their spread to distant sites of the body is the leading cause of mortality in metastatic cancer patients. Metastatic cancer cells invade surrounding tissues and blood vessels by forming F-actin-rich protrusions known as invadopodia, which degrade the extracellular matrix and enable invasion of tumor cells through it. Invadopodia have now been observed in vivo, and recent evidence demonstrates direct molecular links between assembly of invadopodia and cancer metastasis in both mouse models and in human patients...
July 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/29857816/how-mutations-shape-p53-interactions-with-the-genome-to-promote-tumorigenesis-and-drug-resistance
#10
Thorsten Stiewe, Tali E Haran
The tumor suppressive transcription factor p53 regulates a wide array of cellular processes that confer upon cells an essential protection against cancer development. Wild-type p53 regulates gene expression by directly binding to DNA in a sequence-specific manner. p53 missense mutations are the most common mutations in malignant cells and can be regarded as synonymous with anticancer drug resistance and poor prognosis. The current review provides an overview of how the extraordinary variety of more than 2000 different mutant p53 proteins, known as the p53 mutome, affect the interaction of p53 with DNA...
May 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/29857815/fighting-bacterial-persistence-current-and-emerging-anti-persister-strategies-and-therapeutics
#11
REVIEW
Valerie Defraine, Maarten Fauvart, Jan Michiels
In addition to the well-known strategies of antibiotic resistance and biofilm formation, bacterial populations possess an additional survival strategy to endure hostile environments or antibiotic exposure. A small fraction of transiently antibiotic-tolerant phenotypical variants, called persister cells, is capable of surviving treatment with high doses of antibiotics. When antibiotic pressure drops, persisters that switch back to a normal phenotype can resume growth, ensuring survival of the bacterial population...
May 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/29857814/how-the-warburg-effect-supports-aggressiveness-and-drug-resistance-of-cancer-cells
#12
Philippe Icard, Seth Shulman, Diana Farhat, Jean-Marc Steyaert, Marco Alifano, Hubert Lincet
Cancer cells employ both conventional oxidative metabolism and glycolytic anaerobic metabolism. However, their proliferation is marked by a shift towards increasing glycolytic metabolism even in the presence of O2 (Warburg effect). HIF1, a major hypoxia induced transcription factor, promotes a dissociation between glycolysis and the tricarboxylic acid cycle, a process limiting the efficient production of ATP and citrate which otherwise would arrest glycolysis. The Warburg effect also favors an intracellular alkaline pH which is a driving force in many aspects of cancer cell proliferation (enhancement of glycolysis and cell cycle progression) and of cancer aggressiveness (resistance to various processes including hypoxia, apoptosis, cytotoxic drugs and immune response)...
May 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/29680499/corrigendum-to-hepatitis-c-virus-drug-resistance-associated-substitutions-and-their-clinical-relevance-update-2018-drug-resist-updates-37-march-2018-17-39
#13
Maria C Sorbo, Valeria Cento, Velia C Di Maio, Anita Y M Howe, Federico Garcia, Carlo F Perno, Francesca Ceccherini-Silberstein
No abstract text is available yet for this article.
April 18, 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/29548479/thymidine-kinase-and-protein-kinase-in-drug-resistant-herpesviruses-heads-of-a-lernaean-hydra
#14
Dimitri Topalis, Sarah Gillemot, Robert Snoeck, Graciela Andrei
Herpesviruses thymidine kinase (TK) and protein kinase (PK) allow the activation of nucleoside analogues used in anti-herpesvirus treatments. Mutations emerging in these two genes often lead to emergence of drug-resistant strains responsible for life-threatening diseases in immunocompromised populations. In this review, we analyze the binding of different nucleoside analogues to the TK active site of the three α-herpesviruses [Herpes Simplex Virus 1 and 2 (HSV-1 and HSV-2) and Varicella-Zoster Virus (VZV)] and present the impact of known mutations on the structure of the viral TKs...
March 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/29525636/hepatitis-c-virus-drug-resistance-associated-substitutions-and-their-clinical-relevance-update-2018
#15
REVIEW
Maria C Sorbo, Valeria Cento, Velia C Di Maio, Anita Y M Howe, Federico Garcia, Carlo F Perno, Francesca Ceccherini-Silberstein
Nowadays, due to the development of potent Direct-Acting Antiviral Agents (DAAs) that specifically target NS3, NS5A and NS5B viral proteins, several new and highly efficacious options to treat chronic Hepatitis C virus (HCV) infection are available. The natural presence of resistance associated substitutions (RASs), as well as their rapid emergence during incomplete drug-pressure, are intrinsic characteristics of HCV that greatly affect treatment outcome and the chances to achieve a virolgical cure. To date, a high number of RASs in NS3, NS5A, and NS5B have been associated in vivo and/or in vitro with reduced susceptibility to DAAs, but no comprehensive RASs list is available...
March 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/29499837/redundant-angiogenic-signaling-and-tumor-drug-resistance
#16
Rajesh N Gacche, Yehuda G Assaraf
Angiogenesis research in the past two decades has contributed significantly towards understanding the molecular pathophysiology of cancer progression and inspired target-oriented research and pharma industry for the development of novel anti-angiogenic agents. Currently, over eleven drugs targeting angiogenesis have been approved by the FDA for the treatment of various malignancies. Of the registered anti-angiogenic clinical trials until the end of 2017 (ClinicalTrials.gov), over 47% were completed, 10% were terminated, 3% withdrawn, over 0...
January 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/29499836/new-tools-for-old-drugs-functional-genetic-screens-to-optimize-current-chemotherapy
#17
Nora M Gerhards, Sven Rottenberg
Despite substantial advances in the treatment of various cancers, many patients still receive anti-cancer therapies that hardly eradicate tumor cells but inflict considerable side effects. To provide the best treatment regimen for an individual patient, a major goal in molecular oncology is to identify predictive markers for a personalized therapeutic strategy. Regarding novel targeted anti-cancer therapies, there are usually good markers available. Unfortunately, however, targeted therapies alone often result in rather short remissions and little cytotoxic effect on the cancer cells...
January 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/29499835/an-update-on-%C3%AE-lactamase-inhibitor-discovery-and-development
#18
REVIEW
Jean-Denis Docquier, Stefano Mangani
Antibiotic resistance, and the emergence of pan-resistant clinical isolates, seriously threatens our capability to treat bacterial diseases, including potentially deadly hospital-acquired infections. This growing issue certainly requires multiple adequate responses, including the improvement of both diagnosis methods and use of antibacterial agents, and obviously the development of novel antibacterial drugs, especially active against Gram-negative pathogens, which represent an urgent medical need. Considering the clinical relevance of both β-lactam antibiotics and β-lactamase-mediated resistance, the discovery and development of combinations including a β-lactamase inhibitor seems to be particularly attractive, despite being extremely challenging due to the enormous diversity, both structurally and mechanistically, of the potential β-lactamase targets...
January 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/29499834/targeting-bacterial-energetics-to-produce-new-antimicrobials
#19
REVIEW
Kiel Hards, Gregory M Cook
From the war on drug resistance, through cancer biology, even to agricultural and environmental protection: there is a huge demand for rapid and effective solutions to control infections and diseases. The development of small molecule inhibitors was once an accepted "one-size fits all" approach to these varied problems, but persistence and resistance threaten to return society to a pre-antibiotic era. Only five essential cellular targets in bacteria have been developed for the majority of our clinically-relevant antibiotics...
January 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/29145973/tak-ing-aim-at-chemoresistance-the-emerging-role-of-map3k7-as-a-target-for-cancer-therapy
#20
Raffaela Santoro, Carmine Carbone, Geny Piro, Paul J Chiao, Davide Melisi
Cellular drug resistance remains the main obstacle to the clinical efficacy of cancer chemotherapy. Alterations in key pathways regulating cell cycle checkpoints, apoptosis and Epithelial to Mesenchymal Transition (EMT), such as the Mitogen-activated protein kinase (MAPK) pathway, appear to be closely associated to cancer chemoresistance. Transforming growth factor-β (TGF-β)- activated kinase 1 (TAK1, also known as MAP3K7) is a serine/threonine kinase in the mitogen-activated protein kinase (MAP3K) family...
November 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
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