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Nature Reviews. Genetics Aug 2015Drug therapy has a crucial role in the treatment of viral, bacterial, fungal and protozoan infections, as well as the control of human cancer. The success of therapy is... (Review)
Review
Drug therapy has a crucial role in the treatment of viral, bacterial, fungal and protozoan infections, as well as the control of human cancer. The success of therapy is being threatened by the increasing prevalence of resistance. We examine and compare mechanisms of drug resistance in these diverse biological systems (using HIV and Plasmodium falciparum as examples of viral and protozoan pathogens, respectively) and discuss how factors — such as mutation rates, fitness effects of resistance, epistasis and clonal interference — influence the evolutionary trajectories of drug-resistant clones. We describe commonalities and differences related to resistance development that could guide strategies to improve therapeutic effectiveness and the development of a new generation of drugs.
Topics: Chromosomal Instability; Drug Resistance; Drug Therapy; Epistasis, Genetic; Evolution, Molecular; Genetic Fitness; HIV-1; Humans; Models, Biological; Mutation Rate; Neoplasms; Plasmodium falciparum
PubMed: 26149714
DOI: 10.1038/nrg3922 -
Drug Development Research Feb 2019The relentless rise of antibiotic resistance is considered one of the most serious problems facing mankind. This mini-review will cover three cutting-edge approaches... (Review)
Review
The relentless rise of antibiotic resistance is considered one of the most serious problems facing mankind. This mini-review will cover three cutting-edge approaches that use light-based techniques to kill antibiotic-resistant microbial species, and treat localized infections. First, we will discuss antimicrobial photodynamic inactivation using rationally designed photosensitizes combined with visible light, with the added possibility of strong potentiation by inorganic salts such as potassium iodide. Second, the use of blue and violet light alone that activates endogenous photoactive porphyrins within the microbial cells. Third, it is used for "safe UVC" at wavelengths between 200 nm and 230 nm that can kill microbial cells without damaging host mammalian cells. We have gained evidence that all these approaches can kill multidrug resistant bacteria in vitro, and they do not induce themselves any resistance, and moreover can treat animal models of localized infections caused by resistant species that can be monitored by noninvasive bioluminescence imaging. Light-based antimicrobial approaches are becoming a growing translational part of anti-infective treatments in the current age of resistance.
Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Bacterial; Electromagnetic Fields; Humans; Light; Photochemotherapy; Photosensitizing Agents
PubMed: 30070718
DOI: 10.1002/ddr.21453 -
Proceedings. Biological Sciences Mar 2017Why is drug resistance common and vaccine resistance rare? Drugs and vaccines both impose substantial pressure on pathogen populations to evolve resistance and indeed,... (Review)
Review
Why is drug resistance common and vaccine resistance rare? Drugs and vaccines both impose substantial pressure on pathogen populations to evolve resistance and indeed, drug resistance typically emerges soon after the introduction of a drug. But vaccine resistance has only rarely emerged. Using well-established principles of population genetics and evolutionary ecology, we argue that two key differences between vaccines and drugs explain why vaccines have so far proved more robust against evolution than drugs. First, vaccines tend to work prophylactically while drugs tend to work therapeutically. Second, vaccines tend to induce immune responses against multiple targets on a pathogen while drugs tend to target very few. Consequently, pathogen populations generate less variation for vaccine resistance than they do for drug resistance, and selection has fewer opportunities to act on that variation. When vaccine resistance has evolved, these generalities have been violated. With careful forethought, it may be possible to identify vaccines at risk of failure even before they are introduced.
Topics: Drug Resistance, Microbial; Evolution, Molecular; Vaccines
PubMed: 28356449
DOI: 10.1098/rspb.2016.2562 -
Nanoscale Sep 2022Multidrug resistance (MDR) is one of the main reasons for the failure of tumor chemotherapy and has a negative influence on the therapeutic effect. MDR is primarily... (Review)
Review
Multidrug resistance (MDR) is one of the main reasons for the failure of tumor chemotherapy and has a negative influence on the therapeutic effect. MDR is primarily attributable to two mechanisms: the activation of efflux pumps for drugs, which can transport intracellular drug molecules from cells, and other mechanisms not related to efflux pumps, , apoptosis prevention, strengthened DNA repair, and strong oxidation resistance. Nanodrug-delivery systems have recently attracted much attention, showing some unparalleled advantages such as drug targeting and reduced drug efflux, drug toxicity and side effects in reversing MDR. Notably, in drug-delivery platforms based on nanotechnology, multiple therapeutic strategies are integrated into one system, which can compensate for the limitations of individual strategies. In this review, the mechanisms of tumor MDR as well as common vectors and nanocarrier-combined therapy strategies to reverse MDR were summarized to promote the understanding of the latest progress in improving the efficiency of chemotherapy and synergistic strategies. In particular, the adoption of nanotechnology has been highlighted and the principles underlying this phenomenon have been elucidated, which may provide guidance for the development of more effective anticancer strategies.
Topics: Antineoplastic Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Nanotechnology; Neoplasms; Pharmaceutical Preparations
PubMed: 36056710
DOI: 10.1039/d2nr04418h -
BMC Biology Feb 2018Paraphrasing Dobzhansky's famous dictum, I discuss how interrogating cancer through the lens of evolution has transformed our understanding of its development, causality... (Review)
Review
Paraphrasing Dobzhansky's famous dictum, I discuss how interrogating cancer through the lens of evolution has transformed our understanding of its development, causality and treatment resistance. The emerging picture of cancer captures its extensive diversity and therapeutic resilience, highlighting the need for more innovative approaches to control.
Topics: Animals; Biological Evolution; Drug Resistance; Humans; Mutation; Neoplasms; Selection, Genetic
PubMed: 29466995
DOI: 10.1186/s12915-018-0493-8 -
Current Topics in Medicinal Chemistry 2017Despite a reduction in the global burden of malaria, the disease remains responsible for 214 million cases and 438,000 deaths annually with 88% of the mortality... (Review)
Review
BACKGROUND
Despite a reduction in the global burden of malaria, the disease remains responsible for 214 million cases and 438,000 deaths annually with 88% of the mortality occurring in sub-Saharan Africa. Malaria control largely depends on effective chemotherapy. However, the historic and current emergence and spread of multi-drug resistant parasite strains provides significant challenges to malaria control and consequently, reduction of malaria-associated morbidity and mortality. Combating parasite drug resistance requires pharmacological compounds that target both known and novel metabolic pathways that are crucial for parasite survival. In addition, the identification of novel therapeutic agents that target distinct molecular pathways, apart from those of the conventional antimalarials, offers an approach for minimizing drug resistance.
CONCLUSION
This review summarizes current anti-malarial approaches and strategies, therapeutic efficacy for conventional and non-conventional antimalarials, parasitic targets, and the mechanisms responsible for the development of drug resistance.
Topics: Animals; Antimalarials; Drug Discovery; Drug Resistance; Humans; Plasmodium
PubMed: 28137233
DOI: 10.2174/1568026617666170130115323 -
Acta Tropica Mar 2019Antimicrobial resistance (AMR) threatens the prevention and treatment of infections caused by a large range of microorganisms. Leishmania is not an exception and... (Meta-Analysis)
Meta-Analysis Review
Antimicrobial resistance (AMR) threatens the prevention and treatment of infections caused by a large range of microorganisms. Leishmania is not an exception and treatment failure due to drug-resistant organisms is increasingly reported. Currently, no molecular methods and marker are validated to track drug-resistant organism and antimicrobial susceptibility tests are roughly not amenable to a clinical setting. Taking these facts into account, it is essential to reflect on ways to translate basic knowledge into methodologies aimed to diagnose leishmania drug resistance. As a matter of fact, a meta-analysis of the literature discloses the reliability of the promastigotes antimicrobial susceptibility tests (AST) to predict intracellular amastigotes susceptibility status. Promastigote cultures that are easy to perform, typically inexpensive and amenable to standardization should represent a candidate to diagnose resistance. Using AST performed on promastigote, we propose a way to improve leishmania drug resistance diagnosis in the framework of guidance and guideline of the bacterial drug resistance diagnosis. In this review, we highlight challenges that remained and discuss the definition of clinical breakpoints, including the epidemiological cutoff (ECOFF), to track drug-resistant isolates. Our analysis paves the ways to standardize and analyze anti-leishmania susceptibility tests output in order to guide the characterization of drug-resistant isolates, the clinical decision during treatment and the search for new molecular markers.
Topics: Animals; Antiprotozoal Agents; Drug Resistance; Humans; Leishmania; Leishmaniasis, Visceral; Phenotype; Reproducibility of Results
PubMed: 30639471
DOI: 10.1016/j.actatropica.2019.01.009 -
The Journal of Infectious Diseases May 2023
Topics: Humans; Plasmodium vivax; Mefloquine; Plasmodium cynomolgi; Antimalarials; Malaria, Vivax; Drug Resistance; Drug Resistance, Multiple
PubMed: 36478038
DOI: 10.1093/infdis/jiac470 -
European Journal of Medicinal Chemistry Sep 2022Chemotherapy is one of the most common treatments for cancer that uses one or more anti-cancer drugs as a part of the standardized chemotherapy regimen. Cytotoxic... (Review)
Review
Chemotherapy is one of the most common treatments for cancer that uses one or more anti-cancer drugs as a part of the standardized chemotherapy regimen. Cytotoxic chemicals delay and prevent cancer cells from multiplying, invading, and metastasizing. However, the significant drawbacks of cancer chemotherapy are the lack of selectivity of the cytotoxic drugs to tumour cells and normal cells and the development of resistance by cells for the particular drug or the combination of drugs. Multidrug resistance (MDR) is the low sensitivity of specific cells against drugs associated with cancer chemotherapy. The most common mechanisms of anticancer drug resistance are: (a) drug-dependent MDR (b) target-dependent MDR, and (c) drug target-independent MDR. In all the factors, the overexpression of multidrug efflux systems contributes significantly to the increased resistance in the cancer cells. Multidrug resistance due to efflux of anticancer drugs by membrane ABC transporters includes ABCB1, ABCC1, and ABCG2. ABCB1 inhibition can restore the sensitivity of the cancerous cells toward chemotherapeutic drugs. In this review, we discussed ABCB1 inhibitors under clinical studies with their mode of action, potency and selectivity. Also, we have highlighted the contribution of repurposing drugs, biologics and nano formulation strategies to combat multidrug resistance by modulating the ABCB1 activity.
Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Antineoplastic Agents; Cell Line, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Neoplasms
PubMed: 35751979
DOI: 10.1016/j.ejmech.2022.114542 -
Journal of Pharmaceutical and... Jul 2020Drug resistance is worldwide health care crisis which decrease drug efficacy and developing toxicities. Effective resistance detection techniques could alleviate... (Review)
Review
Drug resistance is worldwide health care crisis which decrease drug efficacy and developing toxicities. Effective resistance detection techniques could alleviate treatment cost and mortality associated with this crisis. In this review, the conventional and modern analysis methods for monitoring of drug resistance are presented. Also, various types of emerging rapid and sensitive techniques including electrochemical, electrical, optical and nano-based methods for the screening of drug resistance were discussed. Applications of various methods for the sensitive and rapid detection of drug resistance are investigated. The review outlines existing key issues in the determination which must be overcome before any of these techniques becomes a feasible method for the rapid detection of drug resistance. In this review, the roles of nanomaterials on development of novel methods for the monitoring of drug resistance were presented. Also, limitations and challenges of conventional and modern methods were discussed.
Topics: Animals; Drug Resistance; Drug Resistance, Microbial; Drug-Related Side Effects and Adverse Reactions; Electrochemical Techniques; Humans; Nanotechnology
PubMed: 32283481
DOI: 10.1016/j.jpba.2020.113265