Correlation between the Warburg effect and progression of triple-negative breast cancer DOI Creative Commons
Shaojun Liu, Yuxuan Li, Meng Yuan

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 27, 2023

Triple-negative breast cancer (TNBC) is ineligible for hormonal therapy and Her-2-targeted due to the negative expression of estrogen receptor, progesterone human epidermal growth factor receptor-2. Although targeted immunotherapy have been shown attenuate aggressiveness TNBC partially, few patients benefited from them. The conventional treatment remains chemotherapy. Chemoresistance, however, impedes therapeutic progress over time, chemotherapy toxicity increases burden on patients. Therefore, introducing more advantageous options a necessity. Metabolic reprogramming centered glucose metabolism considered hallmark tumors. It described as tumor cells tend convert lactate even under normoxic conditions, phenomenon known Warburg effect. Similar Darwinian evolution, its emergence attributed selective pressures formed by hypoxic microenvironment pre-malignant lesions. Of note, effect does not disappear with changes in after formation malignant phenotypes. Instead, it forms constitutive mediated mutations or epigenetic modifications, providing robust survival advantage primary metastatic Expanding evidence has demonstrated that mediates multiple invasive behaviors TNBC, including proliferation, metastasis, recurrence, immune escape, multidrug resistance. Moreover, effect-targeted testified be feasible inhibiting progression. However, all TNBCs are sensitive glycolysis inhibitors because flexibly switch their metabolic patterns cope different pressures, namely plasticity. Between medicines actual curative effect, plasticity creates divide must continuously researched bridged.

Language: Английский

Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics DOI Creative Commons
Hao-Ran Jin, Jin Wang, Zijing Wang

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Sept. 12, 2023

Abstract Lipid metabolic reprogramming is an emerging hallmark of cancer. In order to sustain uncontrolled proliferation and survive in unfavorable environments that lack oxygen nutrients, tumor cells undergo transformations exploit various ways acquiring lipid increasing oxidation. addition, stromal immune the microenvironment also reprogramming, which further affects functional phenotypes responses. Given metabolism plays a critical role supporting cancer progression remodeling microenvironment, targeting pathway could provide novel approach treatment. This review seeks to: (1) clarify overall landscape mechanisms cancer, (2) summarize landscapes within their roles progression, (3) potential therapeutic targets for metabolism, highlight combining such approaches with other anti-tumor therapies new opportunities patients.

Language: Английский

Citations

135
Activating cGAS-STING pathway with ROS-responsive nanoparticles delivering a hybrid prodrug for enhanced chemo-immunotherapy DOI Creative Commons
Lei Cao, Huixiang Tian,

Man Fang

et al.

Biomaterials, Journal Year: 2022, Volume and Issue: 290, P. 121856 - 121856

Published: Oct. 18, 2022

cGAS-STING pathway, as an essential intracellular immune response has attracted much attention in tumor immunotherapy. However, low metabolic stability of conventional STING agonists limits their clinical application. Recent study shows that chemotherapeutic drugs cisplatin and camptothecin (CPT) can activate pathway induce by DNA damage. Nevertheless, the ability to is so weak new strategies are required improve drug delivery efficiency for enhanced damage, then efficiently pathway. Herein, we have developed a hybrid platinum prodrug (CPT-Pt (IV)) which be triggered release CPT cells. CPT-Pt (IV) with high hydrophobicity further self-assembled ROS sensitive polymer (P1) mPEG2k-DSPE into responsive nanoparticles (NPs). NPs could accumulate site CPT, resulting double damage finally activating inducing DC cells maturation increasing infiltration CD8+ T on colorectal cancer mouse model. This showed common targeted situ via nano system, enhance effect chemotherapy immunotherapy, provide strategy antitumor therapy.

Language: Английский

Citations

98
New insights into antiangiogenic therapy resistance in cancer: Mechanisms and therapeutic aspects DOI
Maohua Huang, Yuning Lin, Chenran Wang

et al.

Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 64, P. 100849 - 100849

Published: June 30, 2022

Language: Английский

Citations

97
Emerging therapies in cancer metabolism DOI Creative Commons
Yi Xiao, Tian‐Jian Yu, Ying Xu

et al.

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(8), P. 1283 - 1303

Published: Aug. 1, 2023

Language: Английский

Citations

91
Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein DOI Creative Commons
Chenmala Karthika, R. Sureshkumar, Mehrukh Zehravi

et al.

Life, Journal Year: 2022, Volume and Issue: 12(6), P. 897 - 897

Published: June 15, 2022

P-glycoprotein (P-gp) is a major factor in the multidrug resistance phenotype cancer cells. P-gp protein that regulates ATP-dependent efflux of wide range anticancer medicines and confers resistance. Due to its specificity, several attempts have been made block action restore efficacy drugs. The goal has create molecules either compete with for transport or function as direct inhibitor. Despite significant vitro success, there are presently no drugs available clinic can "block" P-gp-mediated Toxicity, unfavourable pharmacological interactions, variety pharmacokinetic difficulties might all be reason failure. On other hand, effect body. It protects vital organs from entry foreign bodies toxic chemicals. Hence, inhibitors should not hinder normal To develop an effective inhibitor P-gp, thorough background knowledge needed this field. main aim review article was set forth merits demerits on cells well influence drug delivery contribution activating were also mentioned.

Language: Английский

Citations

82
Metabolic Reprogramming Driven by IGF2BP3 Promotes Acquired Resistance to EGFR Inhibitors in Non–Small Cell Lung Cancer DOI Open Access
Ziyou Lin, Jingwei Li, Jian Zhang

et al.

Cancer Research, Journal Year: 2023, Volume and Issue: 83(13), P. 2187 - 2207

Published: April 16, 2023

Abstract Acquired resistance represents a bottleneck for effective molecular targeted therapy in lung cancer. Metabolic adaptation is distinct hallmark of human cancer that might contribute to acquired resistance. In this study, we discovered novel mechanism EGFR tyrosine kinase inhibitors (TKI) mediated by IGF2BP3-dependent cross-talk between epigenetic modifications and metabolic reprogramming through the IGF2BP3–COX6B2 axis. IGF2BP3 was upregulated patients with TKI-resistant non–small cell cancer, high expression correlated reduced overall survival. Upregulated RNA binding protein cells sensitivity TKI treatment exacerbated development drug via promoting oxidative phosphorylation (OXPHOS). COX6B2 mRNA bound IGF2BP3, required increased OXPHOS EGFR-TKI IGF2BP3. Mechanistically, 3′-untranslated region an m6A-dependent manner increase stability. Moreover, axis regulated nicotinamide metabolism, which can alter promote Inhibition IACS-010759, small-molecule inhibitor, resulted strong growth suppression vitro vivo gefitinib-resistant patient-derived xenograft model. Collectively, these findings suggest plays critical role confers targetable vulnerability overcome EGFR-TKIs Significance: stabilizes drive provides therapeutic strategy targeting transitions.

Language: Английский

Citations

52
Writers, readers, and erasers RNA modifications and drug resistance in cancer DOI Creative Commons
Di Chen, Xinyu Gu,

Yeltai Nurzat

et al.

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

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

Citations

18
Tumor microenvironment targeted nano-drug delivery systems for multidrug resistant tumor therapy DOI Creative Commons

Xinyue Shao,

Xiaoling Zhao, Binghao Wang

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1689 - 1714

Published: Jan. 2, 2025

In recent years, nano-drug delivery systems (Nano-DDS) that target the tumor microenvironment (TME) to overcome multidrug resistance (MDR) have become a research hotspot in field of cancer therapy. By precisely targeting TME and regulating its unique pathological features, such as hypoxia, weakly acidic pH, abnormally expressed proteins, etc., these Nano-DDS enable effective therapeutic agents reversal MDR. This scientific community is increasing investment development diversified exploring their anti-drug potential. Therefore, it particularly important conduct comprehensive review progress TME-targeted years. After brief introduction MDR, design principle structure liposomes, polymer micelles inorganic nanocarriers are focused on, characteristics described. It also demonstrates how break through MDR treatment various mechanisms, discusses synthetic innovation, results overcoming mechanisms. The was concluded with deliberations on key challenges future outlooks

Language: Английский

Citations

3
The role of extracellular vesicles in the transfer of drug resistance competences to cancer cells DOI Creative Commons
Cristina P. R. Xavier,

Dimas Carolina Belisario,

Rita Rebelo

et al.

Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 62, P. 100833 - 100833

Published: April 5, 2022

Drug resistance remains a major hurdle to successful cancer treatment, being accountable for approximately 90% of cancer-related deaths. In the past years, increasing attention has been given role extracellular vesicles (EVs) in horizontal transfer drug cancer. Indeed, many studies have described dissemination therapy traits mediated by EVs, which may be transferred from resistant tumor cells their sensitive counterparts. Importantly, different key players identified cargo those such as efflux pumps, oncoproteins, antiapoptotic proteins, or microRNAs, among others. Interestingly, EVs-mediated crosstalk between microenvironment (TME) and emerged another important mechanism that leads resistance. Recently, TME-derived EVs responsible also become focus attention. addition, possible mechanisms involved sequestration likely contribute resistance, are discussed herein. Despite latest scientific advances field this is still challenging area research, particularly clinical setting. Therefore, further investigation needed assess relevance failure patients identify biomarkers EV's cargo, develop effective therapeutic strategies surmount This up-to-date review summarizes relevant literature on competences cells, TME process. Finally, knowledge integrated with discussion future applications

Language: Английский

Citations

60
Targeting metabolism to overcome cancer drug resistance: A promising therapeutic strategy for diffuse large B cell lymphoma DOI

Manfei Pi,

Huixian Kuang,

Chunyan Yue

et al.

Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 61, P. 100822 - 100822

Published: March 1, 2022

Language: Английский

Citations

58