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Biomedicine & Pharmacotherapy =... Sep 2023Drug resistance is the main obstacle to achieving a cure in many cancer patients. Reactive oxygen species (ROS) are master regulators of cancer development that act... (Review)
Review
Drug resistance is the main obstacle to achieving a cure in many cancer patients. Reactive oxygen species (ROS) are master regulators of cancer development that act through complex mechanisms. Remarkably, ROS levels and antioxidant content are typically higher in drug-resistant cancer cells than in non-resistant and normal cells, and have been shown to play a central role in modulating drug resistance. Therefore, determining the underlying functions of ROS in the modulation of drug resistance will contribute to develop therapies that sensitize cancer resistant cells by leveraging ROS modulation. In this review, we summarize the notable literature on the sources and regulation of ROS production and highlight the complex roles of ROS in cancer chemoresistance, encompassing transcription factor-mediated chemoresistance, maintenance of cancer stem cells, and their impact on the tumor microenvironment. We also discuss the potential of ROS-targeted therapies in overcoming tumor therapeutic resistance.
Topics: Humans; Reactive Oxygen Species; Drug Resistance, Neoplasm; Neoplasms; Tumor Microenvironment
PubMed: 37354814
DOI: 10.1016/j.biopha.2023.115036 -
Cancer Metastasis Reviews Mar 2024Metabolic reprogramming, a hallmark of cancer, allows cancer cells to adapt to their specific energy needs. The Warburg effect benefits cancer cells in both hypoxic... (Review)
Review
Metabolic reprogramming, a hallmark of cancer, allows cancer cells to adapt to their specific energy needs. The Warburg effect benefits cancer cells in both hypoxic and normoxic conditions and is a well-studied reprogramming of metabolism in cancer. Interestingly, the alteration of other metabolic pathways, especially lipid metabolism has also grabbed the attention of scientists worldwide. Lipids, primarily consisting of fatty acids, phospholipids and cholesterol, play essential roles as structural component of cell membrane, signalling molecule and energy reserves. This reprogramming primarily involves aberrations in the uptake, synthesis and breakdown of lipids, thereby contributing to the survival, proliferation, invasion, migration and metastasis of cancer cells. The development of resistance to the existing treatment modalities poses a major challenge in the field of cancer therapy. Also, the plasticity of tumor cells was reported to be a contributing factor for the development of resistance. A number of studies implicated that dysregulated lipid metabolism contributes to tumor cell plasticity and associated drug resistance. Therefore, it is important to understand the intricate reprogramming of lipid metabolism in cancer cells. In this review, we mainly focused on the implication of disturbed lipid metabolic events on inducing tumor cell plasticity-mediated drug resistance. In addition, we also discussed the concept of lipid peroxidation and its crucial role in phenotypic switching and resistance to ferroptosis in cancer cells. Elucidating the relationship between lipid metabolism, tumor cell plasticity and emergence of resistance will open new opportunities to develop innovative strategies and combinatorial approaches for the treatment of cancer.
Topics: Humans; Lipid Metabolism; Cell Plasticity; Neoplasms; Drug Resistance, Neoplasm; Cholesterol
PubMed: 38438800
DOI: 10.1007/s10555-024-10170-1 -
Biomedicine & Pharmacotherapy =... Oct 2023Despite continuous improvements in research and new cancer therapeutics, the goal of eradicating cancer remains elusive because of drug resistance. For a long time, drug... (Review)
Review
Despite continuous improvements in research and new cancer therapeutics, the goal of eradicating cancer remains elusive because of drug resistance. For a long time, drug resistance research has been focused on tumor cells themselves; however, recent studies have found that the tumor microenvironment also plays an important role in inducing drug resistance. Cancer-associated fibroblasts (CAFs) are a main component of the tumor microenvironment. They cross-talk with cancer cells to support their survival in the presence of anticancer drugs. This review summarizes the current knowledge of the role of CAFs in tumor drug resistance. An in-depth understanding of the mechanisms underlying the cross-talk between CAFs and cancer cells and insight into the importance of CAFs in drug resistance can guide the development of new anticancer strategies.
Topics: Cancer-Associated Fibroblasts; Drug Resistance, Neoplasm; Knowledge; Tumor Microenvironment; Neoplasms
PubMed: 37660643
DOI: 10.1016/j.biopha.2023.115425 -
International Journal of Molecular... Aug 2023Cisplatin is a first-line clinical agent used for treating solid tumors. Cisplatin damages the DNA of tumor cells and induces the production of high levels of reactive... (Review)
Review
Cisplatin is a first-line clinical agent used for treating solid tumors. Cisplatin damages the DNA of tumor cells and induces the production of high levels of reactive oxygen species to achieve tumor killing. Tumor cells have evolved several ways to tolerate this damage. Extracellular vesicles (EVs) are an important mode of information transfer in tumor cells. EVs can be substantially activated under cisplatin treatment and mediate different responses of tumor cells under cisplatin treatment depending on their different cargoes. However, the mechanism of action of tumor-cell-derived EVs under cisplatin treatment and their potential cargoes are still unclear. This review considers recent advances in cisplatin-induced release of EVs from tumor cells, with the expectation of providing a new understanding of the mechanisms of cisplatin treatment and drug resistance, as well as strategies for the combined use of cisplatin and other drugs.
Topics: Humans; Cisplatin; Extracellular Vesicles; Drug Resistance; Neoplasms; Reactive Oxygen Species
PubMed: 37569723
DOI: 10.3390/ijms241512347 -
Cell Reports Oct 2023Acquired drug resistance is a major problem in the treatment of cancer. hTERT-immortalized, untransformed RPE-1 cells can acquire resistance to Taxol by derepressing the...
Acquired drug resistance is a major problem in the treatment of cancer. hTERT-immortalized, untransformed RPE-1 cells can acquire resistance to Taxol by derepressing the ABCB1 gene, encoding for the multidrug transporter P-gP. Here, we investigate how the ABCB1 gene is derepressed. ABCB1 activation is associated with reduced H3K9 trimethylation, increased H3K27 acetylation, and ABCB1 displacement from the nuclear lamina. While altering DNA methylation and H3K27 methylation had no major impact on ABCB1 expression, nor did it promote resistance, disrupting the nuclear lamina component Lamin B Receptor did promote the acquisition of a Taxol-resistant phenotype in a subset of cells. CRISPRa-mediated gene activation supported the notion that lamina dissociation influences ABCB1 derepression. We propose a model in which nuclear lamina dissociation of a repressed gene allows for its activation, implying that deregulation of the 3D genome topology could play an important role in tumor evolution and the acquisition of drug resistance.
Topics: Humans; Drug Resistance, Neoplasm; Paclitaxel; Drug Resistance, Multiple; Neoplasms; DNA Methylation; Cell Line, Tumor
PubMed: 37733591
DOI: 10.1016/j.celrep.2023.113124 -
Emergency Medicine Clinics of North... May 2024(Basic awareness and understanding of antimicrobial resistance and prevailing mechanisms can aid emergency physicians in providing appropriate care to patients with... (Review)
Review
(Basic awareness and understanding of antimicrobial resistance and prevailing mechanisms can aid emergency physicians in providing appropriate care to patients with infections due to a multidrug-resistant organism (MDRO). Empiric treatment of MDRO infections should be approached with caution and guided by the most likely pathogens based on differential diagnosis, severity of the illness, suspected source of infection, patient-specific factors, and local antibiotic susceptibility patterns. Newer broad-spectrum antibiotics should be reserved for critically ill patients where there is a high likelihood of infection with an MDRO.).
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Emergency Service, Hospital
PubMed: 38641399
DOI: 10.1016/j.emc.2024.02.005 -
Blood Jan 2024
Topics: Humans; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Drug Resistance, Neoplasm; Chronic Disease; Recurrence; T-Lymphocytes; RNA-Binding Proteins
PubMed: 38270944
DOI: 10.1182/blood.2023022490 -
International Journal of Molecular... Jul 2023Antimicrobial resistance is presently one of the greatest threats to public health. The excessive and indiscriminate use of antibiotics imposes a continuous selective...
Antimicrobial resistance is presently one of the greatest threats to public health. The excessive and indiscriminate use of antibiotics imposes a continuous selective pressure that triggers the emergence of multi-drug resistance. We performed a large-scale analysis of closed bacterial genomes to identify multi-drug resistance considering the ResFinder antimicrobial classes. We found that more than 95% of the genomes harbor genes associated with resistance to disinfectants, glycopeptides, macrolides, and tetracyclines. On average, each genome encodes resistance to more than nine different classes of antimicrobial drugs. We found higher-than-expected co-occurrences of resistance genes in both plasmids and chromosomes for several classes of antibiotic resistance, including classes categorized as critical according to the World Health Organization (WHO). As a result of antibiotic-resistant priority pathogens, higher-than-expected co-occurrences appear in plasmids, increasing the potential for resistance dissemination. For the first time, co-occurrences of antibiotic resistance have been investigated for priority pathogens as defined by the WHO. For critically important pathogens, co-occurrences appear in plasmids, not in chromosomes, suggesting that the resistances may be epidemic and probably recent. These results hint at the need for new approaches to treating infections caused by critically important bacteria.
Topics: Genome, Bacterial; Plasmids; Anti-Bacterial Agents; Computational Biology; Drug Resistance, Multiple; Drug Resistance, Multiple, Bacterial; Drug Resistance, Bacterial
PubMed: 37511196
DOI: 10.3390/ijms241411438 -
Drug Discovery Today Sep 2023Drug resistance causes catastrophic cancer treatment failures. Mutations in target proteins with altered drug binding indicate a main mechanism of cancer drug resistance... (Review)
Review
Drug resistance causes catastrophic cancer treatment failures. Mutations in target proteins with altered drug binding indicate a main mechanism of cancer drug resistance (CDR). Global research has generated considerable CDR-related data and well-established knowledge bases and predictive tools. Unfortunately, these resources are fragmented and underutilized. Here, we examine computational resources for exploring CDR caused by target mutations, analyzing these tools based on their functional characteristics, data capacity, data sources, methodologies and performance. We also discuss their disadvantages and provide examples of how potential inhibitors of CDR have been discovered using these resources. This toolkit is designed to help specialists explore resistance occurrence effectively and to explain resistance prediction to non-specialists easily.
Topics: Humans; Drug Resistance, Neoplasm; Mutation; Proteins; Neoplasms
PubMed: 37379904
DOI: 10.1016/j.drudis.2023.103686 -
Science China. Life Sciences Jan 2024A potential reason for the failure of tumor therapies is treatment resistance. Resistance to chemotherapy, radiotherapy, and immunotherapy continues to be a major... (Review)
Review
A potential reason for the failure of tumor therapies is treatment resistance. Resistance to chemotherapy, radiotherapy, and immunotherapy continues to be a major obstacle in clinic, resulting in tumor recurrence and metastasis. The major mechanisms of therapy resistance are inhibitions of cell deaths, like apoptosis and necrosis, through drug inactivation and excretion, repair of DNA damage, tumor heterogeneity, or changes in tumor microenvironment, etc. Recent studies have shown that ferroptosis play a major role in therapies resistance by inducing phospholipid peroxidation and iron-dependent cell death. Some ferroptosis inducers in combination with clinical treatment techniques have been used to enhance the effect in tumor therapy. Notably, versatile ferroptosis nanoinducers exhibit an extensive range of functions in reversing therapy resistance, including directly triggering ferroptosis and feedback regulation. Herein, we provide a detailed description of the design, mechanism, and therapeutic application of ferroptosis-mediated synergistic tumor therapeutics. We also discuss the prospect and challenge of nanomedicine in tumor therapy resistance by regulating ferroptosis and combination therapy.
Topics: Humans; Drug Resistance, Neoplasm; Ferroptosis; Nanomedicine; Combined Modality Therapy; Neoplasms; Tumor Microenvironment
PubMed: 37728804
DOI: 10.1007/s11427-022-2340-4