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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 -
Revue Medicale Suisse May 2024
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Resistance, Microbial
PubMed: 38717003
DOI: 10.53738/REVMED.2024.20.873.946 -
Reviews in the Neurosciences Jan 2018Artemin (ARTN) is a member of glial cell line-derived neurotrophic factor (GDNF) family of ligands, and its signaling is mediated via a multi-component receptor complex... (Review)
Review
Artemin (ARTN) is a member of glial cell line-derived neurotrophic factor (GDNF) family of ligands, and its signaling is mediated via a multi-component receptor complex including the glycosylphosphatidylinositol-anchored GDNF family receptors a (GFRa1, GFRa3) and RET receptor tyrosine kinase. The major mechanism of ARTN action is via binding to a non-signaling co-receptor. The major function of ARTN is to drive the molecule to induce migration and axonal projection from sympathetic neurons. It also promotes the survival, proliferation and neurite outgrowth of sympathetic neurons in vitro. ARTN triggers oncogenicity and metastasis by the activation of the AKT signaling pathway. Recent studies have reported that the expression of ARTN in hepatocellular carcinoma is associated with increased tumor size, quick relapse and shorter survival. Furthermore, ARTN promotes drug resistance such as antiestrogens, doxorubicin, fulvestrant, paclitaxel, tamoxifen and trastuzumab. Moreover, ARTN also stimulates the radio-therapeutic resistance. This review highlights the proposed roles of ARTN in cancer cells and discusses recent results supporting its emerging role as an oncogenic, metastatic and drug-resisting agent with a special focus on how these new insights may facilitate rational development of ARTN for targeted therapies in the future.
Topics: Animals; Carcinogenesis; Drug Resistance; Glial Cell Line-Derived Neurotrophic Factor; Humans; Neoplasm Metastasis; Nerve Tissue Proteins
PubMed: 28937965
DOI: 10.1515/revneuro-2017-0029 -
Nature Ecology & Evolution Mar 2018
Topics: Drug Resistance; Herbicide Resistance; Insecticide Resistance; Neoplasms
PubMed: 29453351
DOI: 10.1038/s41559-018-0495-5 -
Biomedicine & Pharmacotherapy =... Jun 2023Multi-drug resistance (MDR) in cancer cells, either intrinsic or acquired through various mechanisms, significantly hinders the therapeutic efficacy of drugs. Typically,... (Review)
Review
Multi-drug resistance (MDR) in cancer cells, either intrinsic or acquired through various mechanisms, significantly hinders the therapeutic efficacy of drugs. Typically, the reduced therapeutic performance of various drugs is predominantly due to the inherent over expression of ATP-binding cassette (ABC) transporter proteins on the cell membrane, resulting in the deprived uptake of drugs, augmenting drug detoxification, and DNA repair. In addition to various physiological abnormalities and extensive blood flow, MDR cancer phenotypes exhibit improved apoptotic threshold and drug efflux efficiency. These severe consequences have substantially directed researchers in the fabrication of various advanced therapeutic strategies, such as co-delivery of drugs along with various generations of MDR inhibitors, augmented dosage regimens and frequency of administration, as well as combinatorial treatment options, among others. In this review, we emphasize different reasons and mechanisms responsible for MDR in cancer, including but not limited to the known drug efflux mechanisms mediated by permeability glycoprotein (P-gp) and other pumps, reduced drug uptake, altered DNA repair, and drug targets, among others. Further, an emphasis on specific cancers that share pathogenesis in executing MDR and effluxed drugs in common is provided. Then, the aspects related to various nanomaterials-based supramolecular programmable designs (organic- and inorganic-based materials), as well as physical approaches (light- and ultrasound-based therapies), are discussed, highlighting the unsolved issues and future advancements. Finally, we summarize the review with interesting perspectives and future trends, exploring further opportunities to overcome MDR.
Topics: Humans; Antineoplastic Agents; Drug Resistance, Neoplasm; Drug Resistance, Multiple; ATP-Binding Cassette Transporters; Neoplasms; Pharmaceutical Preparations
PubMed: 37031496
DOI: 10.1016/j.biopha.2023.114643 -
Indian Journal of Gastroenterology :... Dec 2023Helicobacter pylori is the most prevalent chronic bacterial infection, with approximately half of the world's population estimated to be colonized. The World Health... (Review)
Review
Helicobacter pylori is the most prevalent chronic bacterial infection, with approximately half of the world's population estimated to be colonized. The World Health Organization (WHO) has classified Helicobacter pylori as a class-I carcinogen. All main society guidelines recommend its eradication in infected individuals. The global trend indicates that eradication rates are decreasing annually and the likelihood of eradication decreases with each unsuccessful therapeutic attempt. Resistance to antibiotics in H. pylori strains is the leading cause for eradication failure. Still, drug resistance and treatment failure may be complex, multi-dimensional and associated with several other factors. Knowledge of these factors can aid in optimizing eradication rates. This review will focus on the factors associated with refractory H. pylori, with a particular emphasis on antibiotic resistance mechanisms and their clinical implications. Also, the most recent literature and recommendations available for determining an appropriate regimen after the failure of the first attempt at eradication will be discussed.
Topics: Humans; Helicobacter Infections; Helicobacter pylori; Anti-Bacterial Agents; Drug Resistance, Microbial; Treatment Failure; Drug Therapy, Combination; Drug Resistance, Bacterial
PubMed: 37737326
DOI: 10.1007/s12664-023-01448-3 -
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 -
European Journal of Medicinal Chemistry Mar 2023
Topics: Humans; Drug Resistance, Multiple; Neoplasms; Drug Resistance, Neoplasm
PubMed: 36738554
DOI: 10.1016/j.ejmech.2023.115173 -
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