Advances in understanding the role of P-gp in doxorubicin resistance: Molecular pathways, therapeutic strategies, and prospects

Drug Discovery Today, Journal Year: 2021, Volume and Issue: 27(2), P. 436 - 455

Published: Oct. 7, 2021

P-glycoprotein (P-gp) is a drug efflux transporter that triggers doxorubicin (DOX) resistance. In this review, we highlight the molecular avenues regulating P-gp, such as Nrf2, HIF-1α, miRNAs, and long noncoding (lnc)RNAs, to reveal their participation in DOX These antitumor compounds genetic tools synergistically reduce P-gp expression. Furthermore, ATP depletion impairs activity enhance of DOX. Nanoarchitectures, including liposomes, micelles, polymeric nanoparticles (NPs), solid lipid nanocarriers, have been developed for co-delivery with anticancer genes enhancing cytotoxicity. Surface modification instance hyaluronic acid (HA), can promote selectivity toward cancer cells. We discuss these aspects focus on expression activity.

Language: Английский

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Extracellular Vesicles: New Classification and Tumor Immunosuppression

Biology, Journal Year: 2023, Volume and Issue: 12(1), P. 110 - 110

Published: Jan. 10, 2023

Extracellular vesicles (EVs) are cell-derived membrane-surrounded carrying various types of molecules. These EV cargoes often used as pathophysiological biomarkers and delivered to recipient cells whose fates altered in local distant tissues. Classical EVs exosomes, microvesicles, apoptotic bodies, while recent studies discovered autophagic EVs, stressed matrix vesicles. Here, we classify classical new non-EV nanoparticles. We also review EVs-mediated intercellular communication between cancer tumor-associated cells, such cancer-associated fibroblasts, adipocytes, blood vessels, lymphatic immune cells. Of note, play crucial roles immunosuppression, evasion, immunotherapy resistance. Thus, change hot tumors into cold ones. Moreover, affect nonimmune promote cellular transformation, including epithelial-to-mesenchymal transition (EMT), chemoresistance, tumor production, destruction biological barriers, angiogenesis, lymphangiogenesis, metastatic niche formation.

Language: Английский

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Understanding and targeting resistance mechanisms in cancer

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 22, 2023

Resistance to cancer therapies has been a commonly observed phenomenon in clinical practice, which is one of the major causes treatment failure and poor patient survival. The reduced responsiveness cells multifaceted that can arise from genetic, epigenetic, microenvironmental factors. Various mechanisms have discovered extensively studied, including drug inactivation, intracellular accumulation by uptake or increased efflux, target alteration, activation compensatory pathways for cell survival, regulation DNA repair death, tumor plasticity, microenvironments (TMEs). To overcome resistance, variety strategies proposed, are designed enhance effectiveness reduce resistance. These include identifying biomarkers predict response new targets, developing targeted drugs, combination targeting multiple signaling pathways, modulating TME. present article focuses on different resistance corresponding tackling approaches with recent updates. Perspectives polytherapy mechanisms, novel nanoparticle delivery systems, advanced design tools overcoming also reviewed.

Language: Английский

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ATP-binding cassette efflux transporters and MDR in cancer

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 28(5), P. 103537 - 103537

Published: Feb. 16, 2023

Language: Английский

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Advances in the structure, mechanism and targeting of chemoresistance-linked ABC transporters

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(11), P. 762 - 779

Published: Sept. 15, 2023

Language: Английский

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Hsa-miR-3178/RhoB/PI3K/Akt, a novel signaling pathway regulates ABC transporters to reverse gemcitabine resistance in pancreatic cancer

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: May 10, 2022

Although gemcitabine has been considered as the first-line drug for advanced pancreatic cancer (PC), development of resistance to severely limits effectiveness this chemotherapy, and underlying mechanism remains unclear. Various factors, such ATP binding cassette (ABC) transporters, microRNAs their downstream signaling pathways are included in chemoresistance gemcitabine. This study investigated potential mechanisms ABC transporters related PC both vivo vitro.Immunohistochemistry Western blotting were applied detect expression transporters. Molecular docking analysis was performed explore whether interacted with Gain-of-function loss-of-function analyses investigate functions hsa-miR-3178 vitro vivo. Bioinformatics analysis, dual-luciferase reporter assay used confirm regulatory hsa-miR-3178.We found that P-gp, BCRP MRP1 highly expressed gemcitabine-resistant tissues cells. revealed can bind Hsa-miR-3178 upregulated PANC-1 cells compared its parental Moreover, we promoted These results also verified by animal experiments. RhoB down-regulated it a target hsa-miR-3178. Kaplan-Meier survival curve showed lower significantly associated poor overall patients. Rescue assays demonstrated could reverse hsa-miR-3178-mediated resistance. Interestingly, activating PI3K/Akt pathway-mediated upregulation transporters.Our indicate promotes via RhoB/PI3K/Akt findings suggest be novel therapeutic overcoming PC.

Language: Английский

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Engineered Exosome for Drug Delivery: Recent Development and Clinical Applications

International Journal of Nanomedicine, Journal Year: 2023, Volume and Issue: Volume 18, P. 7923 - 7940

Published: Dec. 1, 2023

Exosomes are nano-sized membrane vesicles that transfer bioactive molecules between cells and modulate various biological processes under physiological pathological conditions. By applying bioengineering technologies, exosomes can be modified to express specific markers or carry therapeutic cargo emerge as novel platforms for the treatment of cancer, neurological, cardiovascular, immune, infectious diseases. However, there many challenges uncertainties in clinical translation exosomes. This review aims provide an overview recent advances engineered exosomes, with a special focus on methods strategies loading drugs into pros cons different methods, optimization exosome production based encapsulated. Moreover, we also summarize current applications prospects well potential risks limitations need addressed engineering, including standardization preparation engineering protocols, quality quantity control drug release, immunogenicity cytotoxicity Overall, represent exciting frontier nanomedicine, but they still face large-scale production, maintenance storage stability, translation. With continuous this field, exosome-based formulation could offer great promise targeted human

Language: Английский

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Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update

Non-Coding RNA, Journal Year: 2023, Volume and Issue: 9(2), P. 27 - 27

Published: April 13, 2023

Since the discovery of first microRNAs (miRNAs, miRs), understanding miRNA biology has expanded substantially. miRNAs are involved and described as master regulators major hallmarks cancer, including cell differentiation, proliferation, survival, cycle, invasion, metastasis. Experimental data indicate that cancer phenotypes can be modified by targeting expression, because act tumor suppressors or oncogenes (oncomiRs), they have emerged attractive tools and, more importantly, a new class targets for drug development in therapeutics. With use mimics molecules (i.e., small-molecule inhibitors such anti-miRS), these therapeutics shown promise preclinical settings. Some miRNA-targeted been extended to clinical development, mimic miRNA-34 treating cancer. Here, we discuss insights into role other non-coding RNAs tumorigenesis resistance summarize some recent successful systemic delivery approaches developments anticancer development. Furthermore, provide comprehensive overview trials finally list based on miRNAs.

Language: Английский

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Drug resistance in ovarian cancer: from mechanism to clinical trial

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: March 28, 2024

Abstract Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance bottleneck in ovarian treatment. The increasing use novel drugs clinical practice poses challenges for treatment drug-resistant cancer. Continuing to classify drug according type without understanding underlying mechanisms unsuitable current practice. We reviewed literature regarding various and found that main are as follows: abnormalities transmembrane transport, alterations DNA damage repair, dysregulation cancer-associated signaling pathways, epigenetic modifications. methylation, histone modifications noncoding RNA activity, three key classes modifications, constitute pivotal resistance. One can have multiple mechanisms. Moreover, common chemotherapies targeted may cross (overlapping) MicroRNAs (miRNAs) interfere with thus regulate abovementioned pathways. A subclass miRNAs, “epi-miRNAs”, modulate regulators impact therapeutic responses. Thus, we also regulatory influence miRNAs on summarized recent phase I/II trials based multitude new therapies under evaluation, preliminary results encouraging. This review provides insight into classification facilitate successful resistant

Language: Английский

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Utilizing non-coding RNA-mediated regulation of ATP binding cassette (ABC) transporters to overcome multidrug resistance to cancer chemotherapy

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 73, P. 101058 - 101058

Published: Jan. 19, 2024

Language: Английский

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