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Cancer Reports (Hoboken, N.J.) Dec 2022The acquisition of resistance to chemotherapy is a major hurdle in the successful application of cancer therapy. Several anticancer approaches, including chemotherapies,... (Review)
Review
BACKGROUND
The acquisition of resistance to chemotherapy is a major hurdle in the successful application of cancer therapy. Several anticancer approaches, including chemotherapies, radiotherapy, surgery and targeted therapies are being employed for the treatment of cancer. However, cancer cells reprogram themselves in multiple ways to evade the effect of these therapies, and over a period of time, the drug becomes inactive due to the development of multi-drug resistance (MDR). MDR is a complex phenomenon where malignant cells become insensitive to anticancer drugs and attain the ability to survive even after several exposures of anticancer drugs. In this review, we have discussed the molecular and cellular paradigms of multidrug resistance in cancer.
RECENT FINDINGS
An Extensive research in cancer biology revealed that drug resistance in cancer is the result of perpetuated intracellular and extracellular mechanisms such as drug efflux, drug inactivation, drug target alteration, oncogenic mutations, altered DNA damage repair mechanism, inhibition of programmed cell death signaling, metabolic reprogramming, epithelial mesenchymal transition (EMT), inherent cell heterogeneity, epigenetic changes, redox imbalance, or any combination of these mechanisms. An inevitable cross-link between inflammation and drug resistance has been discussed. This review provided insight molecular mechanism to understand the vulnerabilities of cancer cells to develop drug resistance.
CONCLUSION
MDR is an outcome of interplays between multiple intricate pathways responsible for the inactivation of drug and development of resistance. MDR is a major obstacle in regimens of successful application of anti-cancer therapy. An improved understanding of the molecular mechanism of multi drug resistance and cellular reprogramming can provide a promising opportunity to combat drug resistance in cancer and intensify anti-cancer therapy for the upcoming future.
Topics: Humans; Drug Resistance, Neoplasm; Drug Resistance, Multiple; Neoplasms; Antineoplastic Agents; Drug Delivery Systems
PubMed: 33052041
DOI: 10.1002/cnr2.1291 -
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 -
Drug Delivery and Translational Research Jun 2024Antimicrobial resistance and tolerance (AMR&T) are urgent global health concerns, with alarmingly increasing numbers of antimicrobial drugs failing and a corresponding... (Review)
Review
Antimicrobial resistance and tolerance (AMR&T) are urgent global health concerns, with alarmingly increasing numbers of antimicrobial drugs failing and a corresponding rise in related deaths. Several reasons for this situation can be cited, such as the misuse of traditional antibiotics, the massive use of sanitizing measures, and the overuse of antibiotics in agriculture, fisheries, and cattle. AMR&T management requires a multifaceted approach involving various strategies at different levels, such as increasing the patient's awareness of the situation and measures to reduce new resistances, reduction of current misuse or abuse, and improvement of selectivity of treatments. Also, the identification of new antibiotics, including small molecules and more complex approaches, is a key factor. Among these, novel DNA- or RNA-based approaches, the use of phages, or CRISPR technologies are some potent strategies under development. In this perspective article, emerging and experienced leaders in drug delivery discuss the most important biological barriers for drugs to reach infectious bacteria (bacterial bioavailability). They explore how overcoming these barriers is crucial for producing the desired effects and discuss the ways in which drug delivery systems can facilitate this process.
Topics: Humans; Anti-Bacterial Agents; Drug Delivery Systems; Animals; Drug Resistance, Microbial; Drug Resistance, Bacterial; Bacteria; Drug Tolerance
PubMed: 38341386
DOI: 10.1007/s13346-023-01513-6 -
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 -
International Journal of Molecular... Nov 2023Drug resistance remains one of the important clinical challenges, making cancer one of the leading causes of death worldwide [...].
Drug resistance remains one of the important clinical challenges, making cancer one of the leading causes of death worldwide [...].
Topics: Humans; Drug Resistance, Neoplasm; Neoplasms
PubMed: 38068907
DOI: 10.3390/ijms242316584 -
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 -
International Journal of Molecular... Feb 2022Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant... (Review)
Review
Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge, as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and the encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer, presents novel nanomedicine therapeutics aimed at improving the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for the clinical application of nanomedicine in the management of LC resistance.
Topics: Antineoplastic Agents; Drug Delivery Systems; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Theranostic Nanomedicine; Tumor Microenvironment
PubMed: 35163777
DOI: 10.3390/ijms23031853 -
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