NOLC1 Suppresses Immuno-chemotherapy by Inhibiting p53-mediated Ferroptosis in Gastric Cancer DOI Open Access

Shengsheng Zhao,

Ji Lin,

Bingzi Zhu

et al.

Published: Dec. 24, 2024

Gastric cancer (GC) is one of the most malignant cancers, and cisplatin (Cis)-based chemotherapy remains main clinical treatment for GC. However, Cis resistance often occurs, largely limiting its therapeutic efficacy in tumors. Therefore, a better understanding drug mechanism could reveal new approaches improving GC efficacy. Here, we define integrative role nucleolar coiled-body phosphoprotein 1 (NOLC1), molecular chaperone that significantly upregulated tissues Cis-resistant cells. Knocking down NOLC1 increased sensitivity to by regulating ferroptosis. Mechanistically, binds p53 DNA binding domain (DBD), decreasing nuclear translocation stimulated suppressing transcriptional functions. Then, p53-mediated ferroptosis suppressed. Furthermore, silence promoted ferroptosis-induced immunogenic cell death (ICD) reprogrammed immunosuppressive tumor microenvironment, thereby increasing anti-programmed death-1 (PD-1) therapy plus Cis. The combination anti-PD-1 effectively inhibited growth without significant side effects. In summary, our findings targeting may be novel strategy increase combined with immune checkpoint inhibitor (ICI) therapy.

Language: Английский

Targeting drug‐tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells DOI Creative Commons
Xiao-Hai Song, Lan Yang, Xiuli Zheng

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(5)

Published: Aug. 24, 2023

Drug resistance remains the greatest challenge in improving outcomes for cancer patients who receive chemotherapy and targeted therapy. Surmounting evidence suggests that a subpopulation of cells could escape intense selective drug treatment by entering drug-tolerant state without genetic variations. These (DTCs) are characterized with slow proliferation rate reversible phenotype. They reside tumor region may serve as reservoir resistant phenotypes. The survival DTCs is regulated epigenetic modifications, transcriptional regulation, mRNA translation remodeling, metabolic changes, antiapoptosis, interactions microenvironment, activation signaling pathways. Thus, targeting regulators opens new avenue therapy-resistant tumors. In this review, we first provide an overview common characteristics regulating networks development. We also discuss potential therapeutic opportunities to target DTCs. Last, current challenges prospects DTC-targeting approach overcome acquired resistance. Reviewing latest developments DTC research be essential discovering methods eliminate DTCs, which represent novel strategy preventing future.

Language: Английский

Citations

11
Genetic Ancestry and Lung Cancer in Latin American Patients: A Crucial Step for Understanding a Diverse Population DOI
Juan Pablo Castañeda-González, Rafael Parra‐Medina, Jonathan W. Riess

et al.

Clinical Lung Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Pharmacological agents targeting drug-tolerant persister cells in cancer DOI Creative Commons
Yu‐Chi Chen, Krishne Gowda, Shantu Amin

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107163 - 107163

Published: April 1, 2024

Current cancer therapy can be effective, but the development of drug resistant disease is usual outcome. These drugs eliminate most tumor burden often fail to rare, "Drug Tolerant Persister" (DTP) cell subpopulations in residual tumors, which referred as "Persister" cells. Therefore, novel therapeutic agents specifically targeting or preventing drug-resistant tumors mediated by remaining persister cells are needed. Since approximately ninety percent cancer-related deaths occur because eventual resistance, identifying, and dissecting biology essential for creation target them. While there remains uncertainty surrounding all markers identifying DTP literature, this review summarizes approaches that available expressing cellular ATP-binding cassette sub-family B member 5 (ABCB5), CD133, CD271, Lysine-specific histone demethylase (KDM5), aldehyde dehydrogenase (ALDH). Persister these were selected focus they have been found on surviving following treatments promote recurrent associated with stem cell-like properties, including self-renewal, differentiation, resistance therapy. The limitations obstacles facing detailed, discussion potential solutions current research areas needing further exploration.

Language: Английский

Citations

3
Targeting of drug-tolerant persister cells as an approach to counter drug resistance in non-small cell lung cancer DOI

Motohiro Izumi,

Daniel B. Costa, Susumu Kobayashi

et al.

Lung Cancer, Journal Year: 2024, Volume and Issue: 194, P. 107885 - 107885

Published: July 8, 2024

Language: Английский

Citations

3
New uracil analog as inhibitor/modulator of ABC transporters or/and NF-κB in taxol-resistant MCF-7/Tx cell line DOI Creative Commons
Angelika Długosz-Pokorska, Tomasz Janecki, Anna Janecka

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(6)

Published: June 25, 2024

Abstract Purpose The global increase in breast cancer cases necessitates ongoing exploration of advanced therapies. Taxol (Tx), an initial treatment, induces mitotic arrest but faces limitations due to side effects and the development resistance. Addressing Tx resistance involves understanding complex molecular mechanisms, including alterations tubulin dynamics, NF-κB signaling, overexpression ABC transporters (ABCB1 ABCG2), leading multidrug (MDR). Methods Real-time PCR ELISA kits were used analyze ABCB1, ABCG2 gene protein expression levels, respectively. An MDR test assessed cell phenotype. Results MCF-7/Tx cells exhibited a 24-fold higher Tx. analysis revealed upregulation ABCG2, NF-κB. U-359 significantly downregulated both ABCB1 levels. Co-incubation with further decreased mRNA these transporters. indicated that increased dye retention, suggesting its potential as inhibitor. Tx, either individually or combined, modulated NF-κBp65 Conclusion Taxol-resistant MCF-7 line provided valuable insights. demonstrated effectiveness reducing NF-κB, solution for overcoming cells. study recommends strategy enhance sensitivity chemotherapy by integrating traditional drugs.

Language: Английский

Citations

1
Metabolic challengers selecting tumor-persistent cells DOI
Caterina Mancini, Giulia Lori, Erica Pranzini

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 35(3), P. 263 - 276

Published: Dec. 9, 2023

Language: Английский

Citations

3
Cellular and Molecular Mechanisms of Chemoresistance for Gastric Cancer DOI Creative Commons
Zonglin Li,

Xingming Shu,

Xin Liu

et al.

International Journal of General Medicine, Journal Year: 2024, Volume and Issue: Volume 17, P. 3779 - 3788

Published: Aug. 1, 2024

Gastric cancer (GC) is one of the most common malignant tumors in digestive tract, and chemotherapy plays an irreplaceable role comprehensive treatment GC. However, chemoresistance makes it difficult for patients with GC to benefit steadily from long term, which ultimately leads tumor recurrence, metastasis, patient death. Elucidating detailed mechanism identifying specific therapeutic targets will help solve problem improve prognosis This review summarizes clarifies cellular molecular mechanisms underlying

Language: Английский

Citations

0
Neuroendocrine transdifferentiation in human cancer: molecular mechanisms and therapeutic targets DOI Creative Commons
Jun Jiang, Donghui Han, Jiawei Wang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Oct. 1, 2024

Abstract Neuroendocrine transdifferentiation (NEtD), also commonly referred to as lineage plasticity, emerges an acquired resistance mechanism molecular targeted therapies in multiple cancer types, predominately occurs metastatic epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung treated with EGFR tyrosine kinase inhibitors and castration‐resistant prostate androgen targeting therapies. NEtD tumors are the lethal histologic subtype unfavorable prognosis limited treatment. A comprehensive understanding of underlying targeted‐induced plasticity could greatly facilitate development novel In past few years, increasingly elegant studies indicated that share key convergent genomic phenotypic characteristics irrespective their site origin, but embrace distinct change function mechanisms. this review, we provide a overview current regulating NEtD, including genetic alterations, DNA methylation, histone modifications, dysregulated noncoding RNA, lineage‐specific transcription factors regulation, other proteomic alterations. We management clinical preclinical practice.

Language: Английский

Citations

0
NOLC1 Suppresses Immuno-chemotherapy by Inhibiting p53-mediated Ferroptosis in Gastric Cancer DOI Creative Commons

Shengsheng Zhao,

Ji Lin,

Bingzi Zhu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 7, 2024

Abstract Gastric cancer (GC) is one of the most malignant cancers, and cisplatin (Cis)-based chemotherapy remains main clinical treatment for GC. However, Cis resistance often occurs, largely limiting its therapeutic efficacy in tumors. Therefore, a better understanding drug mechanism could reveal new approaches improving GC efficacy. Here, we define integrative role nucleolar coiled-body phosphoprotein 1 (NOLC1), molecular chaperone that significantly upregulated tissues Cis-resistant cells. Knocking down NOLC1 increased sensitivity to by regulating ferroptosis. Mechanistically, binds p53 DNA binding domain (DBD), decreasing nuclear translocation stimulated suppressing transcriptional functions. Then, p53-mediated ferroptosis suppressed. Furthermore, silence promoted ferroptosis-induced immunogenic cell death (ICD) reprogrammed immunosuppressive tumor microenvironment, thereby increasing anti-programmed death-1 (PD-1) therapy plus Cis. The combination anti-PD-1 effectively inhibited growth without significant side effects. In summary, our findings targeting may be novel strategy increase combined with immune checkpoint inhibitor (ICI) therapy.

Language: Английский

Citations

0
NOLC1 Suppresses Immuno-chemotherapy by Inhibiting p53-mediated Ferroptosis in Gastric Cancer DOI Open Access

Shengsheng Zhao,

Ji Lin,

Bingzi Zhu

et al.

Published: Dec. 24, 2024

Gastric cancer (GC) is one of the most malignant cancers, and cisplatin (Cis)-based chemotherapy remains main clinical treatment for GC. However, Cis resistance often occurs, largely limiting its therapeutic efficacy in tumors. Therefore, a better understanding drug mechanism could reveal new approaches improving GC efficacy. Here, we define integrative role nucleolar coiled-body phosphoprotein 1 (NOLC1), molecular chaperone that significantly upregulated tissues Cis-resistant cells. Knocking down NOLC1 increased sensitivity to by regulating ferroptosis. Mechanistically, binds p53 DNA binding domain (DBD), decreasing nuclear translocation stimulated suppressing transcriptional functions. Then, p53-mediated ferroptosis suppressed. Furthermore, silence promoted ferroptosis-induced immunogenic cell death (ICD) reprogrammed immunosuppressive tumor microenvironment, thereby increasing anti-programmed death-1 (PD-1) therapy plus Cis. The combination anti-PD-1 effectively inhibited growth without significant side effects. In summary, our findings targeting may be novel strategy increase combined with immune checkpoint inhibitor (ICI) therapy.

Language: Английский

Citations

0