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Praxis Feb 2020
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial
PubMed: 32019456
DOI: 10.1024/1661-8157/a003414 -
Drug Resistance Updates : Reviews and... Jan 2023Drug resistance is well-defined as a serious problem in our living world. To survive, microbes develop defense strategies against antimicrobial drugs. Drugs exhibit less... (Review)
Review
Drug resistance is well-defined as a serious problem in our living world. To survive, microbes develop defense strategies against antimicrobial drugs. Drugs exhibit less or no effective results against microbes after the emergence of resistance because they are unable to cross the microbial membrane, in order to alter enzymatic systems, and/or upregulate efflux pumps, etc. Drug resistance issues can be addressed effectively if a "Resistance-Proof" or "Resistance-Resistant" antimicrobial agent is developed. This article discusses first the need for resistance-proof drugs, the imminent properties of resistance-proof drugs, current and future research progress in the discovery of resistance-proof antimicrobials, the inherent challenges, and opportunities. A molecule having imminent resistance-proof properties could target microbes efficiently, increase potency, and rule out the possibility of early resistance. This review triggers the scientific community to think about how an upsurge in drug resistance can be averted and emphasizes the discussion on the development of next-generation antimicrobials that will provide a novel effective solution to combat the global problem of drug resistance. Hence, resistance-proof drug development is not just a requirement but rather a compulsion in the drug discovery field so that resistance can be battled effectively. We discuss several properties of resistance-proof drugs which could initiate new ways of thinking about next-generation antimicrobials to resolve the drug resistance problem. This article sheds light on the issues of drug resistance and discusses solutions in terms of the resistance-proof properties of a molecule. In summary, the article is a foundation to break new ground in the development of resistance-proof therapeutics in the field of infection biology.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Anti-Infective Agents; Drug Resistance; Drug Discovery
PubMed: 36455341
DOI: 10.1016/j.drup.2022.100890 -
British Journal of Pharmacology Jun 2022In this review, we analyse the impact of oncogenic Ras mutations in mediating cancer drug resistance and the progress made in the abrogation of this resistance, through... (Review)
Review
In this review, we analyse the impact of oncogenic Ras mutations in mediating cancer drug resistance and the progress made in the abrogation of this resistance, through pharmacological targeting. At a physiological level, Ras is implicated in many cellular proliferation and survival pathways. However, mutations within this small GTPase can be responsible for the initiation of cancer, therapeutic resistance and failure, and ultimately disease relapse. Often termed "undruggable," Ras is notoriously difficult to target directly, due to its structure and intrinsic activity. Thus, Ras-mediated drug resistance remains a considerable pharmacological problem. However, with advances in both analytical techniques and novel drug classes, the therapeutic landscape against Ras is changing. Allele-specific, direct Ras-targeting agents have reached clinical trials for the first time, indicating there may, at last, be hope of targeting such an elusive but significant protein for better more effective cancer therapy. LINKED ARTICLES: This article is part of a themed issue on New avenues in cancer prevention and treatment (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc.
Topics: Drug Resistance; Neoplasms
PubMed: 33634485
DOI: 10.1111/bph.15420 -
Nanotechnology Nov 2021Tumor multidrug resistance (MDR) is a phenomenon in which drug-resistant tumor cells are resistant to multiple other unexposed antitumor drugs with different structures... (Review)
Review
Tumor multidrug resistance (MDR) is a phenomenon in which drug-resistant tumor cells are resistant to multiple other unexposed antitumor drugs with different structures and targets. MDR of cancer is a primary cause of clinical chemotherapy failure. With the progress of nanotechnology in the medical field, more and more research works have developed many nanotechnology-based strategies to challenge drug resistance. This review details the recent studies at the National Center for Nanoscience and Technology utilizing various nanochemotherapy strategies for overcoming chemotherapy resistance of tumor. We discuss the benefits and limitations of the diverse strategies, as well as possible ways to overcome these limitations. Importantly, in order to combat cancer chemotherapy resistance with nanomedicine, the mechanisms of drug endocytosis and subsequent fate need to be explored and focused on. In the meanwhile, due to the complexity and diversity of chemotherapy resistance mechanisms, the development of more intelligent and controllable nanodrugs may have greater scope for clinical application.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Mice; Nanomedicine; Nanoparticle Drug Delivery System; Neoplasms; Neoplastic Stem Cells
PubMed: 34700307
DOI: 10.1088/1361-6528/ac3355 -
Life Sciences Jan 2021Cytotoxic drugs remain the first-line option for cancer therapy but the development of drug-resistance by tumor cells represents a primary obstacle for successful... (Review)
Review
Cytotoxic drugs remain the first-line option for cancer therapy but the development of drug-resistance by tumor cells represents a primary obstacle for successful chemotherapy. Autophagy is a physiological mechanism of cell survival efficiently used by tumor cells to avoid cell death and to induce drug-resistance. It is a macromolecular process, in which cells degrade and recycle intracellular substrates and damaged organelles to alleviate cell stress caused by nutritional deprivation, hypoxia, irradiation, and cytotoxic agents, as well. There is evidence that autophagy prevents cancer during the early steps of carcinogenesis, but once transformed, these cells show enhanced autophagy capacity and use it to survive, grow, and facilitate metastasis. Current basic studies and clinical trials show the feasibility of using pharmacological or molecular blockage of autophagy to improve the anticancer therapy efficiency. In this review, we overviewed the pathways and molecular aspects of autophagy, its role in carcinogenesis, and the evidence for its role in cancer adaptation and drug-resistance. Finally, we reviewed the clinical findings on how the autophagy interference helps to improve conventional anticancer therapy.
Topics: Antineoplastic Agents; Autophagy; Cell Death; Cell Survival; Drug Resistance, Neoplasm; Humans; Neoplasms; Signal Transduction
PubMed: 33186569
DOI: 10.1016/j.lfs.2020.118745 -
Molecular Medicine Reports Apr 2020Epilepsy is a common, serious neurological disorder worldwide. Although this disease can be successfully treated in most cases, not all patients respond favorably to... (Review)
Review
Epilepsy is a common, serious neurological disorder worldwide. Although this disease can be successfully treated in most cases, not all patients respond favorably to medical treatments, which can lead to pharmacoresistant epilepsy. Drug‑resistant epilepsy can be caused by a number of mechanisms that may involve environmental and genetic factors, as well as disease‑ and drug‑related factors. In recent years, numerous studies have demonstrated that genetic variation is involved in the drug resistance of epilepsy, especially genetic variations found in drug resistance‑related genes, including the voltage‑dependent sodium and potassium channels genes, and the metabolizer of endogenous and xenobiotic substances genes. The present review aimed to highlight the genetic variants that are involved in the regulation of drug resistance in epilepsy; a comprehensive understanding of the role of genetic variation in drug resistance will help us develop improved strategies to regulate drug resistance efficiently and determine the pathophysiological processes that underlie this common human neurological disease.
Topics: Drug Resistance; Epilepsy; Genetic Variation; Humans
PubMed: 32319641
DOI: 10.3892/mmr.2020.10999 -
Mini Reviews in Medicinal Chemistry 2023Multidrug Resistance (MDR) in tumor cells, a phenomenon in which tumor cells become resistant to chemotherapeutic drugs with different chemical structures and mechanisms...
Multidrug Resistance (MDR) in tumor cells, a phenomenon in which tumor cells become resistant to chemotherapeutic drugs with different chemical structures and mechanisms of action, is a major obstacle to tumor therapy and is an urgent problem to be addressed. Autophagy, widely found in eukaryotic cells, is a lysosome-dependent pathway of self-degradation. In different environments, autophagy can play different roles in the self-protection of cells. At different stages of tumorigenesis, autophagy can play two distinct roles: inhibition of cancer and promotion of cancer. The relationship between autophagy and drug resistance in tumor cells is complex. Moreover, autophagy can play a role in promoting drug resistance and drug sensitivity through different molecular pathways. This study aimed to investigate the relationship between autophagy and drug resistance in tumor cells from the perspective of molecular mechanisms.
Topics: Antineoplastic Agents; Drug Resistance, Neoplasm; Drug Resistance, Multiple; Cell Line, Tumor; Autophagy
PubMed: 36065919
DOI: 10.2174/1389557522666220905090732 -
Current Drug Metabolism 2023Cancer drug resistance remains a difficult barrier to effective treatment, necessitating a thorough understanding of its multi-layered mechanism. (Review)
Review
BACKGROUND
Cancer drug resistance remains a difficult barrier to effective treatment, necessitating a thorough understanding of its multi-layered mechanism.
OBJECTIVE
This study aims to comprehensively explore the diverse mechanisms of cancer drug resistance, assess the evolution of resistance detection methods, and identify strategies for overcoming this challenge. The evolution of resistance detection methods and identification strategies for overcoming the challenge.
METHODS
A comprehensive literature review was conducted to analyze intrinsic and acquired drug resistance mechanisms, including altered drug efflux, reduced uptake, inactivation, target mutations, signaling pathway changes, apoptotic defects, and cellular plasticity. The evolution of mutation detection techniques, encompassing clinical predictions, experimental approaches, and computational methods, was investigated. Strategies to enhance drug efficacy, modify pharmacokinetics, optimizoptimizee binding modes, and explore alternate protein folding states were examined.
RESULTS
The study comprehensively overviews the intricate mechanisms contributing to cancer drug resistance. It outlines the progression of mutation detection methods and underscores the importance of interdisciplinary approaches. Strategies to overcome drug resistance challenges, such as modulating ATP-binding cassette transporters and developing multidrug resistance inhibitors, are discussed. The study underscores the critical need for continued research to enhance cancer treatment efficacy.
CONCLUSION
This study provides valuable insights into the complexity of cancer drug resistance mechanisms, highlights evolving detection methods, and offers potential strategies to enhance treatment outcomes.
Topics: Humans; Drug Resistance, Multiple; Drug Resistance, Neoplasm; ATP-Binding Cassette Transporters; Neoplasms; Biological Transport; Antineoplastic Agents
PubMed: 38141188
DOI: 10.2174/0113892002266408231207150547 -
Science (New York, N.Y.) Feb 2022Machine learning can use clinical history to lower the risk of infection recurrence.
Machine learning can use clinical history to lower the risk of infection recurrence.
Topics: Drug Resistance, Microbial; Machine Learning
PubMed: 35201873
DOI: 10.1126/science.abn9969 -
Journal of Nanobiotechnology Sep 2022Cancer often develops multidrug resistance (MDR) when cancer cells become resistant to numerous structurally and functionally different chemotherapeutic agents. MDR is... (Review)
Review
Cancer often develops multidrug resistance (MDR) when cancer cells become resistant to numerous structurally and functionally different chemotherapeutic agents. MDR is considered one of the principal reasons for the failure of many forms of clinical chemotherapy. Several factors are involved in the development of MDR including increased expression of efflux transporters, the tumor microenvironment, changes in molecular targets and the activity of cancer stem cells. Recently, researchers have designed and developed a number of small molecule inhibitors and derivatives of natural compounds to overcome various mechanisms of clinical MDR. Unfortunately, most of the chemosensitizing approaches have failed in clinical trials due to non-specific interactions and adverse side effects at pharmacologically effective concentrations. Nanomedicine approaches provide an efficient drug delivery platform to overcome the limitations of conventional chemotherapy and improve therapeutic effectiveness. Multifunctional nanomaterials have been found to facilitate drug delivery by improving bioavailability and pharmacokinetics, enhancing the therapeutic efficacy of chemotherapeutic drugs to overcome MDR. In this review article, we discuss the major factors contributing to MDR and the limitations of existing chemotherapy- and nanocarrier-based drug delivery systems to overcome clinical MDR mechanisms. We critically review recent nanotechnology-based approaches to combat tumor heterogeneity, drug efflux mechanisms, DNA repair and apoptotic machineries to overcome clinical MDR. Recent successful therapies of this nature include liposomal nanoformulations, cRGDY-PEG-Cy5.5-Carbon dots and Cds/ZnS core-shell quantum dots that have been employed for the effective treatment of various cancer sub-types including small cell lung, head and neck and breast cancers.
Topics: Antineoplastic Agents; Carbon; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Nanotechnology; Neoplasms; Tumor Microenvironment
PubMed: 36153528
DOI: 10.1186/s12951-022-01626-z