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Expert Opinion on Therapeutic Targets 2023Despite the advances made in cancer treatment in the past decades, therapeutic efficacy is still quite challenging, partially due to the emergence of multidrug... (Review)
Review
INTRODUCTION
Despite the advances made in cancer treatment in the past decades, therapeutic efficacy is still quite challenging, partially due to the emergence of multidrug resistance (MDR). It is crucial to decipher the underlying mechanisms of resistance in order to develop new therapeutic strategies for cancer patients. Previous studies have shown that activation of nuclear factor-κB (NF-κB) plays key roles in various cellular processes including proliferation, anti-apoptosis, metastasis, invasion, and chemoresistance.
AREAS COVERED
In this review, we conduct an integrated analysis of the evidence suggesting the vital roles of the NF-κB signaling pathway in MDR during chemotherapy, immunotherapy, endocrine, and targeted therapy. A literature search was performed on NF-κB and drug resistance in PubMed up to February 2023.
EXPERT OPINION
This review summarizes that the NF-κB signaling pathway exhibits a crucial role in enhancing drug resistance in chemotherapy, immunotherapy, endocrine, and targeted therapy. The application of combination therapy with existing antineoplastic drugs and a safe NF-κB inhibitor could become a promising strategy in cancer treatment. A better understanding of the pathway and mechanisms of drug resistance may help exploit safer and more effective NF-κB-targeting agents for clinical use in the future.
Topics: Humans; NF-kappa B; Signal Transduction; Antineoplastic Agents; Neoplasms; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Cell Line, Tumor
PubMed: 37314372
DOI: 10.1080/14728222.2023.2225767 -
Wiley Interdisciplinary Reviews.... Sep 2021Chemotherapy typically involves the use of specific chemodrugs to inhibit the proliferation of cancer cells, but the frequent emergence of a variety of... (Review)
Review
Chemotherapy typically involves the use of specific chemodrugs to inhibit the proliferation of cancer cells, but the frequent emergence of a variety of multidrug-resistant cancer cells poses a tremendous threat to our combat against cancer. The fundamental causes of multidrug resistance (MDR) have been studied for decades, and can be generally classified into two types: one is associated with the activation of diverse drug efflux pumps, which are responsible for translocating intracellular drug molecules out of the cells; the other is linked with some non-efflux pump-related mechanisms, such as antiapoptotic defense, enhanced DNA repair ability, and powerful antioxidant systems. To overcome MDR, intense efforts have been made to develop synergistic therapeutic strategies by introducing MDR inhibitors or combining chemotherapy with other therapeutic modalities, such as phototherapy, gene therapy, and gas therapy, in the hope that the drug-resistant cells can be sensitized toward chemotherapeutics. In particular, nanotechnology-based drug delivery platforms have shown the potential to integrate multiple therapeutic agents into one system. In this review, the focus was on the recent development of nanostrategies aiming to enhance the efficiency of chemotherapy and overcome the MDR of cancer in a synergistic manner. Different combinatorial strategies are introduced in detail and the advantages as well as underlying mechanisms of why these strategies can counteract MDR are discussed. This review is expected to shed new light on the design of advanced nanomedicines from the angle of materials and to deepen our understanding of MDR for the development of more effective anticancer strategies. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
Topics: Antineoplastic Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Nanomedicine; Neoplasms
PubMed: 33860622
DOI: 10.1002/wnan.1715 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Dec 2020The discovery of antibiotics is a big revolution in human history, and its clinical application has saved countless lives. However, with the widespread and abuse of... (Review)
Review
The discovery of antibiotics is a big revolution in human history, and its clinical application has saved countless lives. However, with the widespread and abuse of antibiotics, many pathogens have developed resistance, and even "Super Bacteria" resistance to multiple drugs have evolved. In the arms race between humans and pathogens, humans are about to face a situation where no medicine is available. Research on microbial antibiotic resistance genes, resistance mechanisms, and the spread of resistance has attracted the attention of many scientific researchers, and various antibiotic resistance gene databases and analysis tools have emerged. In this review, we collect the current databases that focus on antibiotics resistance genes, and discuss these databases in terms of database types, data characteristics, antibiotics resistance gene prediction models and the types of analyzable sequences. In addition, a few gene databases of anti-metal ions and anti-biocides are also involved. It is believed that this summary will provide a reference for how to select and use antibiotic resistance gene databases.
Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Drug Resistance, Microbial; Humans; Metals
PubMed: 33398956
DOI: 10.13345/j.cjb.200375 -
Malaria Journal Mar 2016Plasmodium falciparum resistance to artemisinins, the most potent and fastest acting anti-malarials, threatens malaria elimination strategies. Artemisinin resistance is... (Review)
Review
Plasmodium falciparum resistance to artemisinins, the most potent and fastest acting anti-malarials, threatens malaria elimination strategies. Artemisinin resistance is due to mutation of the PfK13 propeller domain and involves an unconventional mechanism based on a quiescence state leading to parasite recrudescence as soon as drug pressure is removed. The enhanced P. falciparum quiescence capacity of artemisinin-resistant parasites results from an increased ability to manage oxidative damage and an altered cell cycle gene regulation within a complex network involving the unfolded protein response, the PI3K/PI3P/AKT pathway, the PfPK4/eIF2α cascade and yet unidentified transcription factor(s), with minimal energetic requirements and fatty acid metabolism maintained in the mitochondrion and apicoplast. The detailed study of these mechanisms offers a way forward for identifying future intervention targets to fend off established artemisinin resistance.
Topics: Antimalarials; Artemisinins; Drug Resistance; Humans; Malaria, Falciparum; Models, Biological; Plasmodium falciparum
PubMed: 26955948
DOI: 10.1186/s12936-016-1206-9 -
Intensive Care Medicine Dec 2016
Review
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Gram-Negative Bacteria; Humans; Intensive Care Units; Mutation
PubMed: 27647333
DOI: 10.1007/s00134-016-4543-9 -
Current Opinion in Microbiology Oct 2023Our ability to fight infectious diseases is being increasingly compromised due to the emergence and spread of pathogens that become resistant to one or several drugs.... (Review)
Review
Our ability to fight infectious diseases is being increasingly compromised due to the emergence and spread of pathogens that become resistant to one or several drugs. This phenomenon is ubiquitous among pathogens and has parallels in cancer treatment. Given the urgency of the problem, there is a need for a paradigm shift in drug therapy toward one in which the objective to prevent the evolution of drug resistance is considered alongside the main objective of eliminating the infection or tumor. Here, I stress the importance of considering an evolutionary perspective to achieve this goal, and review recent advances in this direction, including therapies that exploit the fitness trade-offs of resistance.
Topics: Drug Resistance; Biological Evolution
PubMed: 37348192
DOI: 10.1016/j.mib.2023.102350 -
PancreasPancreatic ductal adenocarcinoma (PDAC) is one of the leading malignancies affecting human health, largely because of the development of resistance to...
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading malignancies affecting human health, largely because of the development of resistance to chemotherapy/radiotherapy. There are many mechanisms that mediate the development of drug resistance, such as the transport of antineoplastic agents into cells, shifts in energy metabolism and environment, antineoplastic agent-induced DNA damage, and genetic mutations. MicroRNAs are short, noncoding RNAs that are 20 to 24 nucleotides in length and serve several biological functions. They bind to the 3'-untranslated regions of target genes and induce target degradation or translational inhibition. MicroRNAs can regulate several target genes and mediate PDAC chemotherapy/radiotherapy resistance. The detection of novel microRNAs would not only reveal the molecular mechanisms of PDAC and resistance to chemotherapy/radiotherapy but also provide new approaches to PDAC therapy. MicroRNAs are thus potential therapeutic targets for PDAC and might be essential in uncovering new mechanisms of the disease.
Topics: Drug Resistance; Humans; MicroRNAs; Pancreatic Neoplasms; Signal Transduction
PubMed: 35041330
DOI: 10.1097/MPA.0000000000001934 -
Methods in Molecular Biology (Clifton,... 2021The inherent or developed resistance of many cancer cells to chemotherapy and irradiation is actually the main challenge to overcome in cancer treatment. It is well...
The inherent or developed resistance of many cancer cells to chemotherapy and irradiation is actually the main challenge to overcome in cancer treatment. It is well known that cancer cells are characterized by several hallmarks, and it seems that the ability to evolve ways to evade stressful conditions and killing therapies must be consider another typical characteristic displayed by all malignant cells. This overview aims to provide a concise description of the main mechanisms involved in the promotion of resistance to anticancer therapy and to describe the most frequent challenges faced in the war against cancer therapy resistance.
Topics: Antineoplastic Agents; Drug Resistance, Neoplasm; Humans; Immunotherapy; Molecular Targeted Therapy; Neoplasms; Neoplastic Stem Cells; Tumor Hypoxia
PubMed: 32813240
DOI: 10.1007/978-1-0716-0759-6_1 -
International Journal of Molecular... Sep 2022As a result of antibiotic overuse, bacterial antibiotic resistance has become a severe threat to worldwide public health. The development of more effective antimicrobial... (Review)
Review
As a result of antibiotic overuse, bacterial antibiotic resistance has become a severe threat to worldwide public health. The development of more effective antimicrobial therapies and alternative antibiotic strategies is urgently required. The role played by bacterial membrane vesicles (BMVs) in antibiotic resistance has become a current focus of research. BMVs are nanoparticles derived from the membrane components of Gram-negative and Gram-positive bacteria and contain diverse components originating from the cell envelope and cytoplasm. Antibiotic stress stimulates the secretion of BMVs. BMVs promote and mediate antibiotic resistance by multiple mechanisms. BMVs have been investigated as conceptually new antibiotics and drug-delivery vehicles. In this article, we outline the research related to BMVs and antibiotic resistance as a reference for the intentional use of BMVs to combat antibiotic resistance.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Cell Membrane; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial
PubMed: 36232856
DOI: 10.3390/ijms231911553 -
Drug Delivery Dec 2022Chemotherapy for tumors occasionally results in drug resistance, which is the major reason for the treatment failure. Higher drug doses could improve the therapeutic... (Review)
Review
Chemotherapy for tumors occasionally results in drug resistance, which is the major reason for the treatment failure. Higher drug doses could improve the therapeutic effect, but higher toxicity limits the further treatment. For overcoming drug resistance, functional nano-drug delivery system (NDDS) has been explored to sensitize the anticancer drugs and decrease its side effects, which are applied in combating multidrug resistance (MDR) via a variety of mechanisms including bypassing drug efflux, controlling drug release, and disturbing metabolism. This review starts with a brief report on the major MDR causes. Furthermore, we searched the papers from NDDS and introduced the recent advances in sensitizing the chemotherapeutic drugs against MDR tumors. Finally, we concluded that the NDDS was based on several mechanisms, and we looked forward to the future in this field.
Topics: Antineoplastic Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Nanoparticle Drug Delivery System; Nanoparticles; Neoplasms
PubMed: 35616278
DOI: 10.1080/10717544.2022.2079771