Krüppel-like factors in tumors: Key regulators and therapeutic avenues DOI Creative Commons
Yuchen Zhang, Chongjie Yao, Ziyong Ju

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 25, 2023

Krüppel-like factors (KLFs) are a group of DNA-binding transcriptional regulators with multiple essential functions in various cellular processes, including proliferation, migration, inflammation, and angiogenesis. The aberrant expression KLFs is often found tumor tissues for development. At the molecular level, regulate signaling pathways mediate crosstalk among them. Some may also be switches specific biological signals, driving their transition from suppressors to promoters. histological abnormal closely associated cell stemness, apoptosis, alterations microenvironment. Notably, role each KLF tumors varies according type different stages development rather than being invariant. In this review, we focus on advances biology KLFs, particularly regulations several classical by these factors, critical We highlight strong potential as targets therapy suggest directions clinical translational research.

Language: Английский

Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance DOI
Nuray Erin, Jelena Grahovac, Anamaria Brozović

et al.

Drug Resistance Updates, Journal Year: 2020, Volume and Issue: 53, P. 100715 - 100715

Published: June 20, 2020

Language: Английский

Citations

395
The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents DOI Creative Commons
Jiabei Zhou, Yu Kang, Lu Chen

et al.

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 11

Published: March 20, 2020

Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit clinical application of platinum-based treatment. The underlying mechanisms incredibly complicated. Multiple transporters participate active transport antitumor agents, altered expression level, localization, activity may decrease cellular platinum accumulation. Detoxification components, which commonly increasing resistant tumor cells, can efficiently bind to agents prevent formation platinum-DNA adducts, but adducts production is determinant step for cytotoxicity agents. Even if adequate have formed, cells still manage survive through increased DNA repair processes elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum-resistance. This review summarizes critical participators mentioned above highlights most potential therapeutic targets predicted markers. With deeper understanding mechanisms, new solutions would be produced extend largely.

Language: Английский

Citations

384
Drug resistance in cancer: mechanisms and tackling strategies DOI
Tanweer Haider, Vikas Pandey, Nagma Banjare

et al.

Pharmacological Reports, Journal Year: 2020, Volume and Issue: 72(5), P. 1125 - 1151

Published: July 22, 2020

Language: Английский

Citations

220
Cisplatin-resistant NSCLC cells induced by hypoxia transmit resistance to sensitive cells through exosomal PKM2 DOI Creative Commons
Dongliang Wang,

Chaoshuai Zhao,

Fei Xu

et al.

Theranostics, Journal Year: 2021, Volume and Issue: 11(6), P. 2860 - 2875

Published: Jan. 1, 2021

Hypoxia is commonly observed in solid tumors and contributes to the resistance of DNA damage drugs. However, mechanisms behind this are still unclear. In study, we aimed explore effects hypoxia-induced exosomes on non-small cell lung cancer (NSCLC). Methods: NSCLC cells were subjected either normoxic or hypoxic conditions assess survival changes expression levels key proteins. Comparative proteomics performed identify exosomal PKM2 cisplatin-resistant cells-derived exosomes. Functions hypoxia induced-exosomal promoting cisplatin evaluated both vitro vivo experiments molecular demonstrated using flow cytometry, immunoblotting, oxidative stress detection histological examination. A series evaluate function cancer-associated fibroblasts (CAFs). Results: exacerbated due increased that was secreted by cisplatin-resistance cells. We identified transmitted sensitive vivo. Mechanistically, promoted glycolysis produce reductive metabolites, which may neutralize reactive oxygen species (ROS) induced cisplatin. Additionally, inhibited apoptosis a PKM2-BCL2-dependent manner. Moreover, reprogrammed CAFs create an acidic microenvironment proliferation resistance. Conclusions: Our findings revealed transmit delivering PKM2. Exosomal serve as promising biomarker therapeutic target for NSCLC.

Language: Английский

Citations

165
The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer DOI Creative Commons
Chang Liu, Ying Jin, Zhimin Fan

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Sept. 3, 2021

Although chemotherapy can improve the overall survival and prognosis of cancer patients, chemoresistance remains an obstacle due to diversity, heterogeneity, adaptability environmental alters in clinic. To determine more possibilities for therapy, recent studies have begun explore changes metabolism, especially glycolysis. The Warburg effect is a hallmark that refers preference cells metabolize glucose anaerobically rather than aerobically, even under normoxia, which contributes chemoresistance. However, association between glycolysis molecular mechanisms glycolysis-induced unclear. This review describes mechanism from aspects process, signaling pathways, tumor microenvironment, their interactions. understanding how induces may provide new targets concepts therapy.

Language: Английский

Citations

138
Traditional Chinese Medicine has great potential as candidate drugs for lung cancer: A review DOI
Zhicheng Wei, Jing Chen, Fang Zuo

et al.

Journal of Ethnopharmacology, Journal Year: 2022, Volume and Issue: 300, P. 115748 - 115748

Published: Sept. 24, 2022

Language: Английский

Citations

83
Interactions and communications in lung tumor microenvironment: Chemo/radiotherapy resistance mechanisms and therapeutic targets DOI
Feng Yuan, Ying Jiang, Lin Yang

et al.

Journal of drug targeting, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 33

Published: Jan. 15, 2025

The lung tumor microenvironment is composed of various cell types, including cancer cells, stromal and immune as well extracellular matrix (ECM). These cells surrounding ECM create a stiff, hypoxic, acidic, immunosuppressive that can augment the resistance tumors to different forms death facilitate invasion metastasis. This environment induce chemo/radiotherapy by inducing anti-apoptosis mediators such phosphoinositide 3-kinase (PI3K)/Akt, signal transducer activator transcription 3 (STAT3), nuclear factor κB (NF-κB), leading exhaustion antitumor immunity further chemo/radiotherapy. In addition, resist boosting multidrug mechanisms antioxidant defense systems within other TME components. this review, we discuss interactions communications between these components also effects hypoxia, evasion, remodeling on resistance. Finally, review current strategies in preclinical clinical studies, inhibition checkpoint molecules, chemoattractants, cytokines, growth factors, programmed 1 (PD-1), insulin-like 2 (IGF-2) for targeting overcome chemotherapy radiotherapy.

Language: Английский

Citations

2
Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK DOI Open Access
Nurbubu T. Moldogazieva, Innokenty M. Mokhosoev, Alexander A. Terentiev

et al.

Cancers, Journal Year: 2020, Volume and Issue: 12(4), P. 862 - 862

Published: April 2, 2020

It has been long recognized that cancer cells reprogram their metabolism under hypoxia conditions due to a shift from oxidative phosphorylation (OXPHOS) glycolysis in order meet elevated requirements energy and nutrients for proliferation, migration, survival. However, data accumulated over recent years increasingly provided evidence can revert OXPHOS maintain both reprogrammed metabolism, even the same tumor. This phenomenon, denoted as cell metabolic plasticity or hybrid depends on tumor micro-environment is highly heterogeneous influenced by an intensity of vasculature blood flow, oxygen concentration, nutrient supply, requires regulatory interplay between multiple oncogenes, transcription factors, growth reactive species (ROS), among others. Hypoxia-inducible factor-1 (HIF-1) AMP-activated protein kinase (AMPK) represent key modulators switch metabolism. The present review focuses cross-talks HIF-1, glucose transporters (GLUTs), AMPK with other proteins including oncogenes such c-Myc, p53, KRAS; factor-initiated B (PKB)/Akt, phosphatidyl-3-kinase (PI3K), mTOR signaling pathways; suppressors liver B1 (LKB1) TSC1 controlling switches pathways underlie chemo-resistance conventional anti-cancer therapy should be taken into account choosing molecular targets discover novel drugs.

Language: Английский

Citations

136
Metabolic Symbiosis in Chemoresistance: Refocusing the Role of Aerobic Glycolysis DOI Creative Commons

Lisi Ma,

Xiangyun Zong

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: Jan. 24, 2020

Cellular metabolic reprogramming is now recognized as a hallmark of tumors. Altered tumor metabolism determines the malignant biological behaviors and phenotypes cancer. More recently, studies have begun to reveal that cancer cells generally exhibit increased glycolysis or oxidative phosphorylation (OXPHOS) for Adenosine Triphosphate(ATP)generation, which frequently associated with drug resistance. The drug-resistant regulated by PI3K/AKT/mTOR pathway ultimately confer resistance phenotype. key enzymes involved in molecules relevant pathways been used targets reverse In this review, we highlight our current understanding role symbiosis therapeutic discuss ongoing effort develop inhibitors anti-cancer drugs overcome classical chemotherapy.

Language: Английский

Citations

104
The roles and regulation of the KLF5 transcription factor in cancers DOI Creative Commons
Yao Luo, Ceshi Chen

Cancer Science, Journal Year: 2021, Volume and Issue: 112(6), P. 2097 - 2117

Published: April 3, 2021

Krüppel-like factor 5 (KLF5) is a member of the KLF family. Recent studies have suggested that KLF5 regulates expression large number new target genes and participates in diverse cellular functions, such as stemness, proliferation, apoptosis, autophagy, migration. In response to multiple signaling pathways, various transcriptional modulation posttranslational modifications affect level activity KLF5. Several transgenic mouse models revealed physiological pathological functions different cancers. Studies will provide prognostic biomarkers, therapeutic targets, potential drugs for

Language: Английский

Citations

96