-
Molecular Oncology Feb 2024Drug resistance represents a major limitation to the long-term efficacy of anti-cancer treatments. The commonly accepted view is that the selection of inheritable...
Drug resistance represents a major limitation to the long-term efficacy of anti-cancer treatments. The commonly accepted view is that the selection of inheritable genetic mechanisms governs the development of secondary resistance. However, compelling evidence suggests an important role for adaptive cell plasticity and non-genetic mechanisms in the development of therapy resistance. The two phenomena are not mutually exclusive and the interplay between genetic and non-genetic mechanisms may affect tumor evolution during treatment. A broader characterization of the genetic and non-genetic mechanisms of drug resistance may pave the way for more precise and effective therapeutic strategies to overcome resistance.
Topics: Humans; Neoplasms; Drug Resistance; Epigenesis, Genetic; Drug Resistance, Neoplasm
PubMed: 38308461
DOI: 10.1002/1878-0261.13601 -
Journal of Clinical Pharmacy and... Oct 2019Aspirin resistance refers to a patient's poor response to aspirin. There are many factors that can contribute to aspirin resistance, including single-nucleotide... (Review)
Review
WHAT IS KNOWN AND OBJECTIVE
Aspirin resistance refers to a patient's poor response to aspirin. There are many factors that can contribute to aspirin resistance, including single-nucleotide polymorphisms, medication compliance, drug-drug interactions and inflammation.
COMMENT
Recently, oxidative stress-induced 8-isoprostaglandin F2α has attracted considerable attention because it is considered as a mechanism of aspirin resistance in many diseases, including coronary artery disease, neurology system disease, metabolic syndrome, cancer, chronic obstructive pulmonary disease and chronic kidney disease. In these diseases, increased oxidative stress may promote platelet activation and reduce the efficacy of aspirin by producing excessive amounts of 8-isoprostaglandin F2α.
WHAT IS NEW AND CONCLUSION
Given the wide clinical use of aspirin, it is essential to understand why some patients do not response to it. This article reviews current research on aspirin resistance mediated by oxidative stress-induced 8-isoprostaglandin F2α.
Topics: Aspirin; Dinoprost; Drug Resistance; Humans; Oxidative Stress
PubMed: 30989683
DOI: 10.1111/jcpt.12838 -
Expert Review of Anti-infective Therapy Aug 2021: The widespread use of antimicrobial drugs during the ongoing coronavirus disease 2019 (COVID-19) pandemic and the likely emergence of antibiotic-resistant... (Review)
Review
: The widespread use of antimicrobial drugs during the ongoing coronavirus disease 2019 (COVID-19) pandemic and the likely emergence of antibiotic-resistant microorganisms is a global health concern. Even before the COVID-19 pandemic, several antimicrobial drugs have lost their efficacy and are no longer useful to treat life-threatening infections. Since the exacerbation of antimicrobial resistance is likely to be another casualty of the COVID-19 pandemic, there is a pressing need to develop innovative strategies to minimize the risk of antimicrobial resistance.: Focusing on the COVID-19 pandemic, I have briefly summarized the current knowledge and challenges in our understanding of antimicrobial resistance, emphasizing quorum sensing and quorum quenching. Our understanding of bacterial communication by quorum sensing to acquire virulence has paved the way to reduce bacterial pathogenicity through quorum quenching. Availability of clinically viable quorum quenching agents would likely to diminish bacterial virulence to create a microenvironment for the host phagocytic cells to reduce bacterial infection.: Future studies that aim to generate clinically useful quorum quenching agents need to be considered. An important benefit of such agents may be a diminished risk of antimicrobial resistance.
Topics: Anti-Bacterial Agents; Bacteria; COVID-19; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Microbial; Humans; Pandemics; Quorum Sensing
PubMed: 33322965
DOI: 10.1080/14787210.2021.1865802 -
MicrobiologyOpen Sep 2020The agricultural ecosystem creates a platform for the development and dissemination of antimicrobial resistance, which is promoted by the indiscriminate use of... (Review)
Review
The agricultural ecosystem creates a platform for the development and dissemination of antimicrobial resistance, which is promoted by the indiscriminate use of antibiotics in the veterinary, agricultural, and medical sectors. This results in the selective pressure for the intrinsic and extrinsic development of the antimicrobial resistance phenomenon, especially within the aquaculture-animal-manure-soil-water-plant nexus. The existence of antimicrobial resistance in the environment has been well documented in the literature. However, the possible transmission routes of antimicrobial agents, their resistance genes, and naturally selected antibiotic-resistant bacteria within and between the various niches of the agricultural environment and humans remain poorly understood. This study, therefore, outlines an overview of the discovery and development of commonly used antibiotics; the timeline of resistance development; transmission routes of antimicrobial resistance in the agro-ecosystem; detection methods of environmental antimicrobial resistance determinants; factors involved in the evolution and transmission of antibiotic resistance in the environment and the agro-ecosystem; and possible ways to curtail the menace of antimicrobial resistance.
Topics: Agriculture; Animals; Anti-Bacterial Agents; Aquaculture; Drug Resistance, Bacterial; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Ecosystem; Farms; Food Chain; Food Safety; Humans; Livestock; Manure; Public Health; Soil
PubMed: 32710495
DOI: 10.1002/mbo3.1035 -
Nature Reviews. Microbiology Oct 2023Antibiotic resistance is currently one of the most important public health problems. The golden age of antibiotic discovery ended decades ago, and new approaches are... (Review)
Review
Antibiotic resistance is currently one of the most important public health problems. The golden age of antibiotic discovery ended decades ago, and new approaches are urgently needed. Therefore, preserving the efficacy of the antibiotics currently in use and developing compounds and strategies that specifically target antibiotic-resistant pathogens is critical. The identification of robust trends of antibiotic resistance evolution and of its associated trade-offs, such as collateral sensitivity or fitness costs, is invaluable for the design of rational evolution-based, ecology-based treatment approaches. In this Review, we discuss these evolutionary trade-offs and how such knowledge can aid in informing combination or alternating antibiotic therapies against bacterial infections. In addition, we discuss how targeting bacterial metabolism can enhance drug activity and impair antibiotic resistance evolution. Finally, we explore how an improved understanding of the original physiological function of antibiotic resistance determinants, which have evolved to reach clinical resistance after a process of historical contingency, may help to tackle antibiotic resistance.
Topics: Humans; Drug Resistance, Microbial; Bacterial Infections; Bacteria; Anti-Bacterial Agents; Biology; Drug Resistance, Bacterial
PubMed: 37208461
DOI: 10.1038/s41579-023-00902-5 -
Proteomics Apr 2022Antibiotic resistance, the ability of a microbial pathogen to evade the effects of antibiotics thereby allowing them to grow under elevated drug concentrations, is an... (Review)
Review
Antibiotic resistance, the ability of a microbial pathogen to evade the effects of antibiotics thereby allowing them to grow under elevated drug concentrations, is an alarming health problem worldwide and has attracted the attention of scientists for decades. On the other hand, the clinical importance of persistence and tolerance as alternative mechanisms for pathogens to survive prolonged lethal antibiotic doses has recently become increasingly appreciated. Persisters and high-tolerance populations are thought to cause the relapse of infectious diseases, and provide opportunities for the pathogens to evolve resistance during the course of antibiotic therapy. Although proteomics and other omics methodology have long been employed to study resistance, its applications in studying persistence and tolerance are still limited. However, due to the growing interest in the topic and recent progress in method developments to study them, there have been some proteomic studies that yield fresh insights into the phenomenon of persistence and tolerance. Combined with the studies on resistance, these collectively guide us to novel molecular targets for the potential drugs for the control of these dangerous pathogens. In this review, we surveyed previous proteomic studies to investigate resistance, persistence, and tolerance mechanisms, and discussed emerging experimental strategies for studying these phenotypes with a combination of adaptive laboratory evolution and high-throughput proteomics.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Drug Resistance, Microbial; Drug Tolerance; Proteomics
PubMed: 35143120
DOI: 10.1002/pmic.202100409 -
Drug Discovery Today Jan 2020Allosteric drugs have several significant advantages over traditional orthosteric drugs, encompassing higher selectivity and lower toxicity. Although allosteric drugs... (Review)
Review
Allosteric drugs have several significant advantages over traditional orthosteric drugs, encompassing higher selectivity and lower toxicity. Although allosteric drugs have potential advantages as therapeutic agents to treat human diseases, allosteric drug-resistance mutations still occur, rendering these drugs ineffective. Here, we review the emergence of allosteric drug-resistance mutations with an emphasis on examples covering clinically important therapeutic targets, including Breakpoint cluster region-Abelson tyrosine kinase (Bcr-Abl), Akt kinase [also called Protein Kinase B (PKB)], isocitrate dehydrogenase (IDH), MAPK/ERK kinase (MEK), and SRC homology 2 domain-containing phosphatase 2 (SHP2). We also discuss challenges associated with tackling allosteric drug resistance and the possible strategies to overcome this issue.
Topics: Drug Discovery; Drug Resistance; Humans; Mutation
PubMed: 31634592
DOI: 10.1016/j.drudis.2019.10.006 -
Trends in Microbiology Apr 2020All cellular membranes have the functionality of generating and maintaining the gradients of electrical and electrochemical potentials. Such potentials were generally... (Review)
Review
All cellular membranes have the functionality of generating and maintaining the gradients of electrical and electrochemical potentials. Such potentials were generally thought to be an essential but homeostatic contributor to complex bacterial behaviors. Recent studies have revised this view, and we now know that bacterial membrane potential is dynamic and plays signaling roles in cell-cell interaction, adaptation to antibiotics, and sensation of cellular conditions and environments. These discoveries argue that bacterial membrane potential dynamics deserve more attention. Here, we review the recent studies revealing the signaling roles of bacterial membrane potential dynamics. We also introduce basic biophysical theories of the membrane potential to the microbiology community and discuss the needs to revise these theories for applications in bacterial electrophysiology.
Topics: Anti-Bacterial Agents; Bacteria; Biofilms; Biophysics; Drug Resistance, Bacterial; Electrophysiology; Eukaryota; Membrane Potentials
PubMed: 31952908
DOI: 10.1016/j.tim.2019.12.008 -
Parasitology International Dec 2022Genetic mapping has been widely employed to search for genes linked to phenotypes/traits of interest. Because of the ease of maintaining rodent malaria parasites in... (Review)
Review
Genetic mapping has been widely employed to search for genes linked to phenotypes/traits of interest. Because of the ease of maintaining rodent malaria parasites in laboratory mice, many genetic crosses of rodent malaria parasites have been performed to map the parasite genes contributing to malaria parasite development, drug resistance, host immune response, and disease pathogenesis. Drs. Richard Carter, David Walliker, and colleagues at the University of Edinburgh, UK, were the pioneers in developing the systems for genetic mapping of malaria parasite traits, including characterization of genetic markers to follow the inheritance and recombination of parasite chromosomes and performing the first genetic cross using rodent malaria parasites. Additionally, many genetic crosses of inbred mice have been performed to link mouse chromosomal loci to the susceptibility to malaria parasite infections. In this chapter, we review and discuss past and recent advances in genetic marker development, performing genetic crosses, and genetic mapping of both parasite and host genes. Genetic mappings using models of rodent malaria parasites and inbred mice have contributed greatly to our understanding of malaria, including parasite development within their hosts, mechanism of drug resistance, and host-parasite interaction.
Topics: Animals; Disease Susceptibility; Drug Resistance; Genetic Markers; Malaria; Mice; Parasites; Rodentia; Virulence
PubMed: 35926693
DOI: 10.1016/j.parint.2022.102637 -
Pharmacological Research Apr 2024Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the... (Review)
Review
Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the growing advances in technologies in isolation and identification of natural products, the potential of natural products in combating cancer multidrug resistance has received substantial attention. Importantly, natural products can impact multiple targets, which can be valuable in overcoming drug resistance from different perspectives. In the current review, we will describe the well-established mechanisms underlying multidrug resistance, and introduce natural products that could target these multidrug resistant mechanisms. Specifically, we will discuss natural compounds such as curcumin, resveratrol, baicalein, chrysin and more, and their potential roles in combating multidrug resistance. This review article aims to provide a systematic summary of recent advances of natural products in combating cancer drug resistance, and will provide rationales for novel drug discovery.
Topics: Humans; Antineoplastic Agents; Biological Products; Neoplasms; Drug Resistance, Multiple; Drug Resistance, Neoplasm
PubMed: 38342327
DOI: 10.1016/j.phrs.2024.107099