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Biomedicine & Pharmacotherapy =... Nov 2023Cancer therapy resistance (CTR) is the development of cancer resistance to multiple therapeutic strategies, which severely affects clinical response and leads to cancer... (Review)
Review
Cancer therapy resistance (CTR) is the development of cancer resistance to multiple therapeutic strategies, which severely affects clinical response and leads to cancer progression, recurrence, and metastasis. N6-methyladenosine (m6A) has been identified as the most common, abundant, and conserved internal transcriptional alterations of RNA modifications, regulating RNA splicing, translation, stabilization, degradation, and gene expression, and is involved in the development and progression of a variety of diseases, including cancer. Recent studies have shown that m6A modifications play a critical role in both cancer development and progression, especially in reversing CTR. Although m6A modifications have great potential in CTR, the specific molecular mechanisms are not fully elucidated. In this review, we summarize the potential molecular mechanisms of m6A modification in CTR. In addition, we update recent advances in natural products from Traditional Chinese Medicines (TCM) and small-molecule lead compounds targeting m6A modifications, and discuss the great potential and clinical implications of these inhibitors targeting m6A regulators and combinations with other therapies to improve clinical efficacy and overcome CTR.
Topics: Humans; Drug Resistance, Neoplasm; Neoplasms; Adenosine; Biological Products
PubMed: 37696088
DOI: 10.1016/j.biopha.2023.115477 -
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 -
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 -
Frontiers in Cellular and Infection... 2023
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; One Health; Genomics
PubMed: 37886664
DOI: 10.3389/fcimb.2023.1294241 -
Epidemiology and Infection May 2024
Topics: Anti-Bacterial Agents; Humans; Drug Resistance, Bacterial; Bacterial Infections; Bacteria
PubMed: 38712589
DOI: 10.1017/S0950268824000530 -
The Lancet. Microbe May 2024
Topics: Humans; Anti-Bacterial Agents; Antimicrobial Stewardship; Drug Resistance, Bacterial; Brain Drain
PubMed: 38677303
DOI: 10.1016/S2666-5247(24)00102-2 -
PeerJ 2023Gene knockout is a widely used method in biology for investigating gene function. Several technologies are available for gene knockout, including zinc-finger nuclease... (Review)
Review
Gene knockout is a widely used method in biology for investigating gene function. Several technologies are available for gene knockout, including zinc-finger nuclease technology (ZFN), suicide plasmid vector systems, transcription activator-like effector protein nuclease technology (TALEN), Red homologous recombination technology, CRISPR/Cas, and others. Of these, Red homologous recombination technology, CRISPR/Cas9 technology, and suicide plasmid vector systems have been the most extensively used for knocking out bacterial drug resistance genes. These three technologies have been shown to yield significant results in researching bacterial gene functions in numerous studies. This study provides an overview of current gene knockout methods that are effective for genetic drug resistance testing in bacteria. The study aims to serve as a reference for selecting appropriate techniques.
Topics: Craniocerebral Trauma; Drug Resistance, Bacterial; Gene Knockout Techniques; Genes, Bacterial; Technology; Transcription Activator-Like Effector Nucleases; Zinc Finger Nucleases; Animals
PubMed: 37605748
DOI: 10.7717/peerj.15790 -
Cell Communication and Signaling : CCS Feb 2024Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer treatment strategies are evolving due to innate and acquired resistance capacity,... (Review)
Review
Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer treatment strategies are evolving due to innate and acquired resistance capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells to survive and progress under unfavorable conditions. Although the mechanism of drug resistance is being widely studied to generate new target-based drugs with better potency than existing ones. However, due to the broader flexibility in acquired drug resistance, advanced therapeutic options with better efficacy need to be explored. Combination therapy is an alternative with a better success rate though the risk of amplified side effects is commonplace. Moreover, recent groundbreaking precision immune therapy is one of the ways to overcome drug resistance and has revolutionized anticancer therapy to a greater extent with the only limitation of being individual-specific and needs further attention. This review will focus on the challenges and strategies opted by cancer cells to withstand the current therapies at the molecular level and also highlights the emerging therapeutic options -like immunological, and stem cell-based options that may prove to have better potential to challenge the existing problem of therapy resistance. Video Abstract.
Topics: Humans; Proteomics; Drug Resistance, Neoplasm; Neoplasms; Antineoplastic Agents
PubMed: 38347575
DOI: 10.1186/s12964-023-01302-1 -
Nature Communications Jul 2023Antibiotic resistance ABC-Fs (ARE ABC-Fs) are translation factors that provide resistance against clinically important ribosome-targeting antibiotics which are...
Antibiotic resistance ABC-Fs (ARE ABC-Fs) are translation factors that provide resistance against clinically important ribosome-targeting antibiotics which are proliferating among pathogens. Here, we combine genetic and structural approaches to determine the regulation of streptococcal ARE ABC-F gene msrD in response to macrolide exposure. We show that binding of cladinose-containing macrolides to the ribosome prompts insertion of the leader peptide MsrDL into a crevice of the ribosomal exit tunnel, which is conserved throughout bacteria and eukaryotes. This leads to a local rearrangement of the 23 S rRNA that prevents peptide bond formation and accommodation of release factors. The stalled ribosome obstructs the formation of a Rho-independent terminator structure that prevents msrD transcriptional attenuation. Erythromycin induction of msrD expression via MsrDL, is suppressed by ectopic expression of mrsD, but not by mutants which do not provide antibiotic resistance, showing correlation between MsrD function in antibiotic resistance and its action on this stalled complex.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Macrolides; Abducens Nerve Diseases; Accommodation, Ocular
PubMed: 37393329
DOI: 10.1038/s41467-023-39553-8 -
Pharmacological Research Apr 2024Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the... (Review)
Review
Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the growing advances in technologies in isolation and identification of natural products, the potential of natural products in combating cancer multidrug resistance has received substantial attention. Importantly, natural products can impact multiple targets, which can be valuable in overcoming drug resistance from different perspectives. In the current review, we will describe the well-established mechanisms underlying multidrug resistance, and introduce natural products that could target these multidrug resistant mechanisms. Specifically, we will discuss natural compounds such as curcumin, resveratrol, baicalein, chrysin and more, and their potential roles in combating multidrug resistance. This review article aims to provide a systematic summary of recent advances of natural products in combating cancer drug resistance, and will provide rationales for novel drug discovery.
Topics: Humans; Antineoplastic Agents; Biological Products; Neoplasms; Drug Resistance, Multiple; Drug Resistance, Neoplasm
PubMed: 38342327
DOI: 10.1016/j.phrs.2024.107099