-
European Journal of Medicinal Chemistry Aug 2021Clinically, chemotherapy is the mainstay in the treatment of multiple cancers. However, highly adaptable and activated survival signaling pathways of cancer cells... (Review)
Review
Clinically, chemotherapy is the mainstay in the treatment of multiple cancers. However, highly adaptable and activated survival signaling pathways of cancer cells readily emerge after long exposure to chemotherapeutics drugs, resulting in multi-drug resistance (MDR) and treatment failure. Recently, growing evidences indicate that the molecular action mechanisms of cancer MDR are closely associated with abnormalities in saccharides. In this review, saccharides affecting cancer MDR development are elaborated and analyzed in terms of aberrant aerobic glycolysis and its related enzymes, abnormal glycan structures and their associated enzymes, and glycoproteins. The reversal strategies including depletion of ATP, circumventing the original MDR pathway, activation by or inhibition of sugar-related enzymes, combination therapy with traditional cytotoxic agents, and direct modification on the sugar moiety, are ultimately proposed. It follows that abnormal saccharides have a significant effect on cancer MDR development, providing a new perspective for overcoming MDR and improving the outcome of chemotherapy.
Topics: Antineoplastic Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Molecular Structure; Neoplasms; Polysaccharides
PubMed: 33933752
DOI: 10.1016/j.ejmech.2021.113487 -
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 -
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 -
Expert Opinion on Drug Discovery Feb 2024Malaria remains a devastating infectious disease with hundreds of thousands of casualties each year. Antimalarial drug resistance has been a threat to malaria control... (Review)
Review
INTRODUCTION
Malaria remains a devastating infectious disease with hundreds of thousands of casualties each year. Antimalarial drug resistance has been a threat to malaria control and elimination for many decades and is still of concern today. Despite the continued effectiveness of current first-line treatments, namely artemisinin-based combination therapies, the emergence of drug-resistant parasites in Southeast Asia and even more alarmingly the occurrence of resistance mutations in Africa is of great concern and requires immediate attention.
AREAS COVERED
A comprehensive overview of the mechanisms underlying the acquisition of drug resistance in is given. Understanding these processes provides valuable insights that can be harnessed for the development and selection of novel antimalarials with reduced resistance potential. Additionally, strategies to mitigate resistance to antimalarial compounds on the short term by using approved drugs are discussed.
EXPERT OPINION
While employing strategies that utilize already approved drugs may offer a prompt and cost-effective approach to counter antimalarial drug resistance, it is crucial to recognize that only continuous efforts into the development of novel antimalarial drugs can ensure the successful treatment of malaria in the future. Incorporating resistance propensity assessment during this developmental process will increase the likelihood of effective and enduring malaria treatments.
Topics: Humans; Antimalarials; Malaria; Plasmodium falciparum; Drug Resistance; Drug Discovery
PubMed: 38108082
DOI: 10.1080/17460441.2023.2284820 -
Seminars in Cancer Biology Dec 2021Platinum is the backbone of systemic treatment in ovarian cancer and development of platinum resistance is associated with poor survival. Here, we perform a... (Review)
Review
Platinum is the backbone of systemic treatment in ovarian cancer and development of platinum resistance is associated with poor survival. Here, we perform a comprehensive review of the literature regarding resistance mechanisms and advances in therapy for platinum resistant ovarian cancer, with a focus on high-grade serous carcinoma. Platinum resistance can be intrinsic or acquired. Resistance mechanisms are complex and diverse. Intracellular mechanisms include restoration of homologous recombination repair, reduced intracellular accumulation of platinum, blocked cellular replication and inhibition of apoptosis. These act in concert with immunosuppressive, angiogenic and stromal changes in the tumour microenvironment to drive treatment resistance. Current molecular stratification lacks prognostic and predictive validity, limited in part by the extreme genomic complexity of high-grade serous ovarian cancer. Clinical trials represent an important option for patients as standard of care treatment options have limited efficacy. The most promising trials appear to focus on rational combinations of chemotherapy, immunotherapy, anti-angiogenics, PARP inhibitors, targeted therapy and/or antibody-drug conjugates. Resistance mechanisms are multifactorial with capacity to evolve over time, making clinical detection challenging. It is increasingly apparent that clinical trials must incorporate correlative studies to elucidate predictive biomarkers. They must also adopt endpoints that can appropriately measure benefit for palliative treatments. Future research must aim to deepen our understanding of the biology of this disease, and deliver meaningful benefit in terms of improved quality of life and overall survival for women with platinum resistant ovarian cancer.
Topics: Animals; Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Drug Resistance, Neoplasm; Female; Humans; Platinum Compounds
PubMed: 32871277
DOI: 10.1016/j.semcancer.2020.08.013 -
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 -
Infectious Disease Clinics of North... Dec 2020
Topics: Animals; Anti-Infective Agents; Bacteria; Centers for Disease Control and Prevention, U.S.; Drug Resistance, Multiple, Bacterial; Drug Resistance, Multiple, Fungal; Fungi; Humans; United States
PubMed: 33131576
DOI: 10.1016/j.idc.2020.09.001 -
Archives of Medical Research Apr 2022One of the most important complications that lead to unsuccessful treatment of cancer is resistance against chemotherapy agents, so called multidrug resistance (MDR)....
OBJECTIVES
One of the most important complications that lead to unsuccessful treatment of cancer is resistance against chemotherapy agents, so called multidrug resistance (MDR). Thus, identification of the novel medications with low side effects and high efficacy to reverse MDR is highly required. Accordingly, the current study was performed to investigate the molecular mechanism of MDR in LS174T and LS174T/Oxaliplatin (OXP) cell lines during treatment with Nitazoxanide (NTZ) in combination with OXP.
MATERIALS AND METHODS
In the present in vitro study, we evaluated the effects of NTZ on the cytotoxicity of OXP using Thiazolyl Blue Tetrazolium Blue (MTT) assay in LS174T and LS174T/OXP cell lines when treated with OXP and NTZ, alone or in combination, for 24 and 48 h incubation. Then, we assessed the changes in the expression level of CTNNB1, ABCB1, c-Myc, and cyclin D1 genes in different treated groups.
RESULTS
Exposure of LS174T/OXP cells to NTZ led to the elevation of cell sensitivity to OXP and induced caspase-3/7 activity, which results in apoptosis. Furthermore, NTZ downregulated Wnt/β-catenin signaling pathway through significant decrease of CTNNB1, c-Myc, ABCB1, and cyclin D1 genes and resulted in drug resistance reversal and inhibition of cell proliferation.
CONCLUSION
These results indicate that Wnt/β-catenin pathway is important in developing cancer and MDR. In this regard, NTZ could reverse MDR in colorectal cancer (CRC) cells by downregulation of Wnt/β-catenin signaling pathway, suggesting that NTZ should be more considered in future studies as a potent adjuvant in CRC chemotherapy.
Topics: Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Neoplasms; Nitro Compounds; Thiazoles; Wnt Signaling Pathway
PubMed: 34937659
DOI: 10.1016/j.arcmed.2021.12.001 -
Frontiers in Cellular and Infection... 2021
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Phylogeny; Virulence; Virulence Factors
PubMed: 33869085
DOI: 10.3389/fcimb.2021.654283