Unveiling the mechanisms and challenges of cancer drug resistance

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 12, 2024

Abstract Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer strategies are evolving due to innate acquired capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells survive progress under unfavorable conditions. Although the mechanism of drug being widely studied generate new target-based drugs with better potency than existing ones. However, broader flexibility in resistance, advanced therapeutic options efficacy need be explored. Combination therapy an alternative a success rate though risk amplified side effects commonplace. Moreover, recent groundbreaking precision immune ways overcome has revolutionized anticancer greater extent only limitation individual-specific needs further attention. This review will focus on challenges opted withstand current therapies at molecular level also highlights emerging -like immunological, stem cell-based may prove have potential challenge problem resistance.

Language: Английский

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Chemical Design of Magnetic Nanomaterials for Imaging and Ferroptosis-Based Cancer Therapy

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Ferroptosis, an iron-dependent form of regulatory cell death, has garnered significant interest as a therapeutic target in cancer treatment due to its distinct characteristics, including lipid peroxide generation and redox imbalance. However, clinical application oncology is currently limited by issues such suboptimal efficacy potential off-target effects. The advent nanotechnology provided new way for overcoming these challenges through the development activatable magnetic nanoparticles (MNPs). These innovative MNPs are designed improve specificity ferroptosis induction. This Review delves into chemical biological principles guiding design ferroptosis-based therapies imaging-guided therapies. It discusses mechanisms attributes ferroptosis, composition MNPs, their mechanism action inducers, integration with advanced imaging techniques monitoring. Additionally, we examine convergence other strategies, chemodynamic therapy, photothermal photodynamic sonodynamic immunotherapy, within context nanomedicine strategies utilizing MNPs. highlights multifunctional surpass limitations conventional treatments, envisioning future drug-resistance-free, precision diagnostics treating recalcitrant cancers.

Language: Английский

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Doxorubicin-loaded micelles in tumor cell-specific chemotherapy

Environmental Research, Journal Year: 2023, Volume and Issue: 227, P. 115722 - 115722

Published: March 21, 2023

Language: Английский

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Nrf2 inhibition increases sensitivity to chemotherapy of colorectal cancer by promoting ferroptosis and pyroptosis

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Sept. 1, 2023

Abstract Oxaliplatin is widely used in chemotherapy for colorectal cancer (CRC), but its sensitivity has become a major obstacle to limiting efficacy. Many literatures reported that Nrf2 activation promoted tumor chemoresistance. In this study, we explored the role and mechanism of inhibition oxaliplatin-based chemosensitivity CRC. vitro experiments, applied 4-octyl itaconate (4-OI) activate Nrf2, lentivirus knock down CRC cell lines. By measuring viability, colony formation, apoptosis, reactive oxygen species production, western blot, found oxaliplatin lobaplatin suppressed growth HCT-116 LOVO cells dose-dependent manner, expression Nrf2. 4-OI, an activator, reduced sensibility lobaplatin, while knockdown lobaplatin. Through public databases, GPX4 normal tissues was lower compared with CRC, high predicted poor prognosis. Meanwhile, vitro. The enhanced effects reduce GSH content, increase MDA which oxaliplatin-induced ferroptosis. Subsequently, GSDME-N, induced LDH, IL-1β, TNF-a release, aggravated occurrence GSMDE-mediated pyroptosis. Finally, on HCT116 xenograft vivo. Thus, our study showed improved by promoting ferroptosis pyroptosis, provided new target overcoming chemoresistance

Language: Английский

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Cancer-associated fibroblasts undergoing neoadjuvant chemotherapy suppress rectal cancer revealed by single-cell and spatial transcriptomics

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(10), P. 101231 - 101231

Published: Oct. 1, 2023

Neoadjuvant chemotherapy (NAC) for rectal cancer (RC) shows promising clinical response. The modulation of the tumor microenvironment (TME) by NAC and its association with therapeutic response remain unclear. Here, we use single-cell RNA sequencing spatial transcriptome to examine cell dynamics in 29 patients RC, who are sampled pairwise before after treatment. We construct a high-resolution cellular dynamic landscape remodeled their associations markedly reshapes populations cancer-associated fibroblasts (CAFs), which is strongly associated CAF subsets regulate TME through recruitment crosstalk activate immunity suppress progression multiple cytokines, including CXCL12, SLIT2, DCN. In contrast, epithelial-mesenchymal transition malignant cells upregulated CAF_FAP MIR4435-2HG induction, resulting worse outcomes. Our study demonstrates that inhibits modulates remodeling CAFs.

Language: Английский

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Theranostics Nanomedicine Applications for Colorectal Cancer and Metastasis: Recent Advances

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 7922 - 7922

Published: April 27, 2023

Colorectal cancer (CRC) is the third most common worldwide, and metastatic CRC a fatal disease. The CRC-affected tissues show several molecular markers that could be used as fresh strategy to create newer methods of treating condition. liver peritoneum are where metastasis occurs frequently. Once tumor has metastasized liver, peritoneal carcinomatosis frequently regarded disease's final stage. However, nearly 50% patients with do not have metastases. New diagnostic therapeutic approaches must developed due poor response present treatment choices in advanced stages necessity an accurate diagnosis early stages. Many unique amazing nanomaterials promise for both may found nanotechnology. Numerous nanoformulations, including carbon nanotubes, dendrimers, liposomes, silica nanoparticles, gold metal-organic frameworks, core-shell polymeric nano-formulations, nano-emulsion systems, among others, can targeted anticancer drug delivery purposes CRC. Theranostic combined nanomedicine been proposed revolutionary approach improve detection treatment. This review highlights recent studies, potential, challenges development nanoplatforms

Language: Английский

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STAT3 as a newly emerging target in colorectal cancer therapy: Tumorigenesis, therapy response, and pharmacological/nanoplatform strategies

Environmental Research, Journal Year: 2023, Volume and Issue: 233, P. 116458 - 116458

Published: June 21, 2023

Language: Английский

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The expression of exosomal and cellular miRNAs in predicting oxaliplatin resistance in colorectal cancer cells: an in silico and in vitro study

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 9, 2025

Colorectal cancer (CRC) is a common gastrointestinal cancer, and even though oxaliplatin chemotherapy effective, there high likelihood of relapse, indicating the presence oxaliplatin-resistant CRC. Therefore, it crucial to comprehend molecular mechanisms resistance develop effective strategies counter drug resistance. Numerous studies have demonstrated close association between microRNAs (miRNAs) in In this study, we aimed identify essential exosomal cellular miRNA related CRC cell line HCT-116. The expression profile cells with was analyzed. effectiveness diagnostics biomarker potency miRNAs were evaluated by receiver operating characteristic (ROC) analysis. Target identified, enrichment analysis assessed based on Gene Ontology (GO), Reactome, Human Disease (DO). vitro experiments, HCT-116 (HCT116-OXA) developed, exosomes isolated characterized from HCT116-OXA HCT116 cells. selected their exosomes, they compared using quantitative real-time PCR. This study revealed that combination miR-4326, miR-3615, miR-7974, miR-130b-3p, miR-454-3p exhibited highest area under curve (AUC), sensitivity, specificity, superior diagnostic predictive performance. displayed reduced early late apoptosis, bypass S phase arrest, prolonged doubling time, higher IC50 parental miR-454-3p, miR-4326 decreased as sensitive However, significantly miR-130b-3p observed low miR-3615 or could predict response therapy. indicates potential these specific serve markers for

Language: Английский

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Amphiphilic polymeric nanodrug integrated with superparamagnetic iron oxide nanoparticles for synergistic antibacterial and antitumor therapy of colorectal cancer

Acta Biomaterialia, Journal Year: 2023, Volume and Issue: 173, P. 432 - 441

Published: Nov. 19, 2023

Language: Английский

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Wnt/β-catenin signalling activates IMPDH2-mediated purine metabolism to facilitate oxaliplatin resistance by inhibiting caspase-dependent apoptosis in colorectal cancer

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 3, 2024

Abstract Background Oxaliplatin resistance usually leads to therapeutic failure and poor prognosis in colorectal cancer (CRC), while the underlying mechanisms are not yet fully understood. Metabolic reprogramming is strongly linked drug resistance, however, role mechanism of metabolic oxaliplatin remain unclear. Here, we aim explore functions purine metabolism on oxaliplatin-induced apoptosis CRC. Methods An oxaliplatin-resistant CRC cell line was generated, untargeted metabolomics analysis conducted. The inosine 5ʹ-monophosphate dehydrogenase type II (IMPDH2) expression lines determined by quantitative real-time polymerase chain reaction (qPCR) western blotting analysis. effects IMPDH2 overexpression, knockdown pharmacological inhibition were assessed flow cytometry vivo vitro. Results revealed that levels metabolites, especially guanosine monophosphate (GMP), markedly elevated cells. accumulation metabolites mainly arose from upregulation expression. Gene set enrichment (GSEA) indicated high correlates with PURINE_METABOLISM MULTIPLE-DRUG-RESISTANCE pathways. cells higher more resistant apoptosis. Overexpression resulted reduced death upon treatment oxaliplatin, whereas led increased sensitivity through influencing activation Caspase 7/8/9 PARP1 proteins Targeted mycophenolic acid (MPA) or mycophenolate mofetil (MMF) enhanced vitro decreased tumour burden when combined treatment. Mechanistically, Wnt/β-catenin signalling hyperactivated cells, a reciprocal positive regulatory existed between IMPDH2. Blocking pathway could resensitize which be restored addition GMP. Conclusions predictive biomarker target for

Language: Английский

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