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Drug Resistance Updates : Reviews and... Jan 2023The binding of programmed death-1 (PD-1) on the surface of T cells and PD-1 ligand 1 (PD-L1) on tumor cells can prevent the immune-killing effect of T cells on tumor... (Review)
Review
The binding of programmed death-1 (PD-1) on the surface of T cells and PD-1 ligand 1 (PD-L1) on tumor cells can prevent the immune-killing effect of T cells on tumor cells and promote the immune escape of tumor cells. Therefore, immune checkpoint blockade targeting PD-1/PD-L1 is a reliable tumor therapy with remarkable efficacy. However, the main challenges of this therapy are low response rate and acquired resistance, so that the outcomes of this therapy are usually unsatisfactory. This review begins with the description of biological structure of the PD-1/PD-L1 immune checkpoint and its role in a variety of cells. Subsequently, the therapeutic effects of immune checkpoint blockers (PD-1 / PD-L1 inhibitors) in various tumors were introduced and analyzed, and the reasons affecting the function of PD-1/PD-L1 were systematically analyzed. Then, we focused on analyzing, sorting out and introducing the possible underlying mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade including abnormal expression of PD-1/PD-L1 and some factors, immune-related pathways, tumor immune microenvironment, and T cell dysfunction and others. Finally, promising therapeutic strategies to sensitize the resistant patients with PD-1/PD-L1 blockade treatment were described. This review is aimed at providing guidance for the treatment of various tumors, and highlighting the drug resistance mechanisms to offer directions for future tumor treatment and improvement of patient prognosis.
Topics: Humans; B7-H1 Antigen; Drug Resistance; Immunotherapy; Neoplasms; Programmed Cell Death 1 Receptor; Tumor Microenvironment; Drug Resistance, Neoplasm
PubMed: 36527888
DOI: 10.1016/j.drup.2022.100907 -
Molecules (Basel, Switzerland) Jan 2022Multidrug resistance is a leading concern in public health. It describes a complex phenotype whose predominant feature is resistance to a wide range of structurally... (Review)
Review
Multidrug resistance is a leading concern in public health. It describes a complex phenotype whose predominant feature is resistance to a wide range of structurally unrelated cytotoxic compounds, many of which are anticancer agents. Multidrug resistance may be also related to antimicrobial drugs, and is known to be one of the most serious global public health threats of this century. Indeed, this phenomenon has increased both mortality and morbidity as a consequence of treatment failures and its incidence in healthcare costs. The large amounts of antibiotics used in human therapies, as well as for farm animals and even for fishes in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs. It is not negligible that the ongoing COVID-19 pandemic may further contribute to antimicrobial resistance. In this paper, multidrug resistance and antimicrobial resistance are underlined, focusing on the therapeutic options to overcome these obstacles in drug treatments. Lastly, some recent studies on nanodrug delivery systems have been reviewed since they may represent a significant approach for overcoming resistance.
Topics: Animals; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Nanoparticle Drug Delivery System
PubMed: 35163878
DOI: 10.3390/molecules27030616 -
International Microbiology : the... Nov 2021We are living in a society of fear, where the objectivity in estimating risks is distorted by the media and the interested parties. During more than half of a century,... (Review)
Review
We are living in a society of fear, where the objectivity in estimating risks is distorted by the media and the interested parties. During more than half of a century, the feeling of antibiotic resistance as an apocalyptic phenomenon able to push our society to the high mortality rates caused by infectious diseases in the dark pre-antibiotic ages has been steadily rising. However, at the current status of modern medicine, at least in the high-medium income countries, mortality by lack of efficacy of the antibiotic armamentarium in the therapy of infections is a problem, but not a catastrophe. The threat of antibiotic resistance has many other aspects than failures of therapy in the individual patient. Among them, the increase in the frequency of severe and potentially lethal infections, as bacteremia, the population biology alterations of the healthy microbiota, the global acceleration of bacterial evolution by selecting natural genetic tools mediating microbial interactions, and, most importantly, by modifying the equilibrium and composition of environmental microbial communities. All these threats have huge implications for human health as members of a Biosphere entirely rooted in a menaced microbiosphere.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Drug Resistance, Microbial; Humans; Microbiota
PubMed: 34028624
DOI: 10.1007/s10123-021-00184-y -
Nature Reviews. Cancer Nov 2023Cancer cells frequently display intrinsic or acquired resistance to chemically diverse anticancer drugs, limiting therapeutic success. Among the main mechanisms of this... (Review)
Review
Cancer cells frequently display intrinsic or acquired resistance to chemically diverse anticancer drugs, limiting therapeutic success. Among the main mechanisms of this multidrug resistance is the overexpression of ATP-binding cassette (ABC) transporters that mediate drug efflux, and, specifically, ABCB1, ABCG2 and ABCC1 are known to cause cancer chemoresistance. High-resolution structures, biophysical and in silico studies have led to tremendous progress in understanding the mechanism of drug transport by these ABC transporters, and several promising therapies, including irradiation-based immune and thermal therapies, and nanomedicine have been used to overcome ABC transporter-mediated cancer chemoresistance. In this Review, we highlight the progress achieved in the past 5 years on the three transporters, ABCB1, ABCG2 and ABCC1, that are known to be of clinical importance. We address the molecular basis of their broad substrate specificity gleaned from structural information and discuss novel approaches to block the function of ABC transporters. Furthermore, genetic modification of ABC transporters by CRISPR-Cas9 and approaches to re-engineer amino acid sequences to change the direction of transport from efflux to import are briefly discussed. We suggest that current information regarding the structure, mechanism and regulation of ABC transporters should be used in clinical trials to improve the efficiency of chemotherapeutics for patients with cancer.
Topics: Humans; ATP-Binding Cassette Transporters; Drug Resistance, Neoplasm; Drug Resistance, Multiple; Antineoplastic Agents
PubMed: 37714963
DOI: 10.1038/s41568-023-00612-3 -
Revue de L'infirmiere Oct 2023
Topics: Humans; Drug Resistance, Microbial
PubMed: 37838362
DOI: 10.1016/j.revinf.2023.08.002 -
Current Opinion in Pharmacology Oct 2020Multiple drug resistance (MDR) is a significant challenge in the treatment of cancer using chemotherapy. There are numerous reasons and mechanisms that are responsible... (Review)
Review
Multiple drug resistance (MDR) is a significant challenge in the treatment of cancer using chemotherapy. There are numerous reasons and mechanisms that are responsible for the development of MDR in cancer tissues. Further, exosomes and its constituents also play a vital role in limiting the efficacy of chemotherapeutic agents. Exosomes are well known for their role in developing resistance in addition to promoting tumor advancement and metastasis. This review discusses the role of exosomes in the development of drug resistance along with their allied mechanisms. This review also discusses the upregulation and downregulation of various exosomal components, which can be effectively employed as diagnostic biomarkers in the treatment of cancer. The essential applications of exosomes to treat drug-resistant cancer have also been discussed.
Topics: Animals; Antineoplastic Agents; Biomarkers; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Exosomes; Humans; Neoplasms; Nucleic Acids; Proteins
PubMed: 33053492
DOI: 10.1016/j.coph.2020.08.017 -
Nature Reviews. Microbiology Jan 2024Antimicrobial resistance (AMR) poses a substantial threat to human health. The widespread prevalence of AMR is, in part, due to the horizontal transfer of antibiotic... (Review)
Review
Antimicrobial resistance (AMR) poses a substantial threat to human health. The widespread prevalence of AMR is, in part, due to the horizontal transfer of antibiotic resistance genes (ARGs), typically mediated by plasmids. Many of the plasmid-mediated resistance genes in pathogens originate from environmental, animal or human habitats. Despite evidence that plasmids mobilize ARGs between these habitats, we have a limited understanding of the ecological and evolutionary trajectories that facilitate the emergence of multidrug resistance (MDR) plasmids in clinical pathogens. One Health, a holistic framework, enables exploration of these knowledge gaps. In this Review, we provide an overview of how plasmids drive local and global AMR spread and link different habitats. We explore some of the emerging studies integrating an eco-evolutionary perspective, opening up a discussion about the factors that affect the ecology and evolution of plasmids in complex microbial communities. Specifically, we discuss how the emergence and persistence of MDR plasmids can be affected by varying selective conditions, spatial structure, environmental heterogeneity, temporal variation and coexistence with other members of the microbiome. These factors, along with others yet to be investigated, collectively determine the emergence and transfer of plasmid-mediated AMR within and between habitats at the local and global scale.
Topics: Animals; Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; One Health; Drug Resistance, Multiple; Plasmids
PubMed: 37430173
DOI: 10.1038/s41579-023-00926-x -
Current Opinion in Structural Biology Feb 2023Robust technology has been developed to systematically quantify fitness landscapes that provide valuable opportunities to improve our understanding of drug resistance... (Review)
Review
Robust technology has been developed to systematically quantify fitness landscapes that provide valuable opportunities to improve our understanding of drug resistance and define new avenues to develop drugs with reduced resistance susceptibility. We outline the critical importance of drug resistance studies and the potential for fitness landscape approaches to contribute to this effort. We describe the major technical advancements in mutational scanning, which is the primary approach used to quantify protein fitness landscapes. There are many complex steps to consider in planning and executing mutational scanning projects including developing a selection scheme, generating mutant libraries, tracking the frequency of variants using next-generation sequencing, and processing and interpreting the data. Key experimental parameters impacting each of these steps are discussed to aid in planning fitness landscape studies. There is a strong need for improved understanding of drug resistance, and fitness landscapes provide a promising new approach.
Topics: Genetic Fitness; Models, Genetic; Mutation; Proteins; Drug Resistance
PubMed: 36621152
DOI: 10.1016/j.sbi.2022.102525 -
Gut Microbes 2023poses a serious threat to public health and socioeconomic development worldwide because of its foodborne pathogenicity and antimicrobial resistance. This... (Review)
Review
poses a serious threat to public health and socioeconomic development worldwide because of its foodborne pathogenicity and antimicrobial resistance. This biofilm-planktonic lifestyle enables to interfere with the host and become resistant to drugs, conferring inherent tolerance to antibiotics. The complex biofilm structure makes bacteria tolerant to harsh conditions due to the diversity of physiological, biochemical, environmental, and molecular factors constituting resistance mechanisms. Here, we provide an overview of the mechanisms of biofilm formation and antibiotic resistance, with an emphasis on less-studied molecular factors and in-depth analysis of the latest knowledge about upregulated drug-resistance-associated genes in bacterial aggregates. We classified and extensively discussed each group of these genes encoding transporters, outer membrane proteins, enzymes, multiple resistance, metabolism, and stress response-associated proteins. Finally, we highlighted the missing information and studies that need to be undertaken to understand biofilm features and contribute to eliminating antibiotic-resistant and health-threatening biofilms.
Topics: Gastrointestinal Microbiome; Biofilms; Drug Resistance, Microbial; Anti-Bacterial Agents; Salmonella; Drug Resistance, Bacterial
PubMed: 37401756
DOI: 10.1080/19490976.2023.2229937 -
Microbial Drug Resistance (Larchmont,... Jan 2021
Topics: Anti-Infective Agents; Drug Industry; Drug Resistance, Microbial; Genes, Bacterial; Humans
PubMed: 33464170
DOI: 10.1089/mdr.2020.29000.igb