Novel betulin derivatives as multidrug reversal agents targeting P-glycoprotein DOI Creative Commons
Jerónimo Laiolo, Dafni G. Graikioti,

Cecilia L. Barbieri

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 2, 2024

Abstract Chemotherapy is a powerful means of cancer treatment but its efficacy compromised by the emergence multidrug resistance (MDR), mainly linked to efflux transporter ABCB1/P-glycoprotein (P-gp). Based on chemical structure betulin, identified in our previous work as an effective modulator P-gp function, series analogs were designed, synthesized and evaluated source novel inhibitors. Compounds 6g 6i inhibited rhodamine 123 overexpressed leukemia cells, K562/Dox, at concentrations 0.19 µM 0.39 µM, respectively, increased intracellular accumulation doxorubicin submicromolar concentration 0.098 µM. able restore sensitivity K562/Dox Dox 0.024 respectively. Structure–activity relationship analysis molecular modeling revealed important information about structural features conferring activity. All active compounds fitted specific region involving transmembrane helices (TMH) 4–6 from one homologous half TMH 7 12 other, also showing close contacts with 6 12. that bound preferentially another inactive, regardless their free energy binding. It should be noted devoid toxic effects against peripheral blood mononuclear normal cells erythrocytes. The data obtained indicates both might proposed scaffolds for obtaining promising inhibitors overcoming MDR.

Language: Английский

Understanding and targeting resistance mechanisms in cancer DOI Creative Commons
Zi‐Ning Lei, Tian Qin,

Qiu‐Xu Teng

et al.

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

Citations

113
ATP-binding cassette efflux transporters and MDR in cancer DOI Open Access

Manasi S. Pote,

Rajesh N. Gacche

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

Published: Feb. 16, 2023

Language: Английский

Citations

97
The Role of Silver Nanoparticles in the Diagnosis and Treatment of Cancer: Are There Any Perspectives for the Future? DOI Creative Commons
Peter Takáč, Radka Michalková, Martina Čižmáriková

et al.

Life, Journal Year: 2023, Volume and Issue: 13(2), P. 466 - 466

Published: Feb. 7, 2023

Cancer is a fatal disease with complex pathophysiology. Lack of specificity and cytotoxicity, as well the multidrug resistance traditional cancer chemotherapy, are most common limitations that often cause treatment failure. Thus, in recent years, significant efforts have concentrated on development modernistic field called nano-oncology, which provides possibility using nanoparticles (NPs) aim to detect, target, treat diseases. In comparison conventional anticancer strategies, NPs provide targeted approach, preventing undesirable side effects. What more, nanoparticle-based drug delivery systems shown good pharmacokinetics precise targeting, reduced resistance. It has been documented that, cells, promote reactive oxygen species (ROS) production, induce cell cycle arrest apoptosis, activate ER (endoplasmic reticulum) stress, modulate various signaling pathways, etc. Furthermore, their ability inhibit tumor growth vivo also documented. this paper, we reviewed role silver (AgNPs) nanomedicine, discussing numerous mechanisms by they render properties under both vitro conditions, potential diagnosis cancer.

Language: Английский

Citations

91
Advances in the structure, mechanism and targeting of chemoresistance-linked ABC transporters DOI
Andaleeb Sajid, Hadiar Rahman, Suresh V. Ambudkar

et al.

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

Published: Sept. 15, 2023

Language: Английский

Citations

73
Recent Advances in Nanomaterials-Based Targeted Drug Delivery for Preclinical Cancer Diagnosis and Therapeutics DOI Creative Commons
Harshita Tiwari, Nilesh Rai, Swati Singh

et al.

Bioengineering, Journal Year: 2023, Volume and Issue: 10(7), P. 760 - 760

Published: June 25, 2023

Nano-oncology is a branch of biomedical research and engineering that focuses on using nanotechnology in cancer diagnosis treatment. Nanomaterials are extensively employed the field oncology because their minute size ultra-specificity. A wide range nanocarriers, such as dendrimers, micelles, PEGylated liposomes, polymeric nanoparticles used to facilitate efficient transport anti-cancer drugs at target tumor site. Real-time labeling monitoring cells quantum dots essential for determining level therapy needed The drug targeted site either by passive or active means. Passive targeting makes use microenvironment enhanced permeability retention effect, while involves ligand-coated nanoparticles. Nanotechnology being diagnose early stage detecting cancer-specific biomarkers imaging. implication employs photoinduced nanosensitizers, reverse multidrug resistance, enabling delivery CRISPR/Cas9 RNA molecules therapeutic applications. However, despite recent advancements nano-oncology, there need delve deeper into domain designing applying improved diagnostics.

Language: Английский

Citations

69
Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes DOI Creative Commons
Huai Liu, Ling Tang, Yanxian Li

et al.

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

Published: Jan. 22, 2024

Abstract The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated almost all the undifferentiated NPC cases. Over past three decades, radiation therapy chemotherapy have formed cornerstone treatment. However, recent advancements in immunotherapy introduced a range promising approaches for managing NPC. In light these developments, it has become evident that deeper understanding tumor microenvironment (TME) crucial. TME serves dual function, acting as promoter tumorigenesis while also orchestrating immunosuppression, thereby facilitating cancer progression enabling immune evasion. Consequently, comprehensive comprehension its intricate involvement initiation, progression, metastasis imperative development effective anticancer drugs. Moreover, given complexity inter-patient heterogeneity, personalized treatment should be designed to maximize therapeutic efficacy circumvent drug resistance. This review aims provide an in-depth exploration within context EBV-induced NPC, particular emphasis on pivotal role regulating intercellular communication shaping responses. Additionally, offers concise summary resistance mechanisms potential strategies their reversal, specifically relation chemoradiation therapy, targeted immunotherapy. Furthermore, advances clinical trials pertaining are discussed.

Language: Английский

Citations

33
Schiff bases and their metal complexes to target and overcome (multidrug) resistance in cancer DOI
Ana Podolski-Renić, Ana Čipak Gašparović, Andreia Valente

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 270, P. 116363 - 116363

Published: March 29, 2024

Language: Английский

Citations

23
Triazole-fused pyrimidines in target-based anticancer drug discovery DOI
Xing‐Jie Dai,

Lei-Peng Xue,

Shi‐Kun Ji

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 249, P. 115101 - 115101

Published: Jan. 11, 2023

Language: Английский

Citations

33
Targeting epidermal growth factor receptor and its downstream signaling pathways by natural products: A mechanistic insight DOI

Rutuja Damare,

Kritika Engle, Gautam Kumar

et al.

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(5), P. 2406 - 2447

Published: March 3, 2024

The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase (RTK) that maintains normal tissues and cell signaling pathways. EGFR overactivated overexpressed in many malignancies, including breast, lung, pancreatic, kidney. Further, the gene mutations protein overexpression activate downstream pathways cancerous cells, stimulating growth, survival, resistance to apoptosis, progression of tumors. Anti-EGFR therapy potential approach for treating malignancies has demonstrated clinical success specific cancers. recent report suggests most clinically used inhibitors developed cancer cells. This perspective provides brief overview its implications cancer. We have summarized natural products-derived anticancer compounds with mechanistic basis tumor inhibition via pathway. propose developing lead molecules into new agents bright future after investigation.

Language: Английский

Citations

12
Anticancer Mechanism of Astragalus Polysaccharide and Its Application in Cancer Immunotherapy DOI Creative Commons
Ziqing He, Xiyu Liu,

Simin Qin

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(5), P. 636 - 636

Published: May 15, 2024

Astragalus polysaccharide (APS) derived from A. membranaceus plays a crucial role in traditional Chinese medicine. These polysaccharides have shown antitumor effects and are considered safe. Thus, they become increasingly important cancer immunotherapy. APS can limit the spread of by influencing immune cells, promoting cell death, triggering autophagy, impacting tumor microenvironment. When used combination with other therapies, enhance treatment outcomes reduce toxicity side effects. combined checkpoint inhibitors, relay cellular immunotherapy, vaccines broadened application immunotherapy enhanced effectiveness. By summarizing research on over past two decades, this review elaborates anticancer mechanism its use clinical trials. Considering multiple roles APS, emphasizes importance using as an adjunct to compares APS. This discussion provides insights into specific action reveals molecular targets for developing effective strategies, highlights wide therapy future.

Language: Английский

Citations

10