Nanomedicines Targeting Metabolic Pathways in the Tumor Microenvironment: Future Perspectives and the Role of AI DOI Creative Commons

Shuai Fan,

Wenyu Wang,

Wieqi Che

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 201 - 201

Published: March 13, 2025

Background: Tumor cells engage in continuous self-replication by utilizing a large number of resources and capabilities, typically within an aberrant metabolic regulatory network to meet their own demands. This dysregulation leads the formation tumor microenvironment (TME) most solid tumors. Nanomedicines, due unique physicochemical properties, can achieve passive targeting certain tumors through enhanced permeability retention (EPR) effect, or active deliberate design optimization, resulting accumulation TME. The use nanomedicines target critical pathways holds significant promise. However, requires careful selection relevant drugs materials, taking into account multiple factors. traditional trial-and-error process is relatively inefficient. Artificial intelligence (AI) integrate big data evaluate delivery efficiency nanomedicines, thereby assisting nanodrugs. Methods: We have conducted detailed review key papers from databases, such as ScienceDirect, Scopus, Wiley, Web Science, PubMed, focusing on reprogramming, mechanisms action development metabolism, application AI empowering nanomedicines. integrated content present current status research metabolism potential future directions this field. Results: Nanomedicines possess excellent TME which be utilized disrupt cells, including glycolysis, lipid amino acid nucleotide metabolism. disruption selective killing disturbance Extensive has demonstrated that AI-driven methodologies revolutionized nanomedicine development, while concurrently enabling precise identification molecular regulators involved oncogenic reprogramming pathways, catalyzing transformative innovations targeted cancer therapeutics. Conclusions: great Additionally, will accelerate discovery metabolism-related targets, empower optimization help minimize toxicity, providing new paradigm for development.

Language: Английский

Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies DOI Creative Commons
Qian Zhou,

Yu Meng,

Daishi Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Language: Английский

Citations

182
Tumor biomarkers for diagnosis, prognosis and targeted therapy DOI Creative Commons
Yue Zhou, Lei Tao, Jiahao Qiu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 20, 2024

Abstract Tumor biomarkers, the substances which are produced by tumors or body’s responses to during tumorigenesis and progression, have been demonstrated possess critical encouraging value in screening early diagnosis, prognosis prediction, recurrence detection, therapeutic efficacy monitoring of cancers. Over past decades, continuous progress has made exploring discovering novel, sensitive, specific, accurate tumor significantly promoted personalized medicine improved outcomes cancer patients, especially advances molecular biology technologies developed for detection biomarkers. Herein, we summarize discovery development including history conventional innovative used biomarker classification biomarkers based on tissue origins, application clinical management. In particular, highlight recent advancements biomarker-based anticancer-targeted therapies emerging as breakthroughs promising strategies. We also discuss limitations challenges that need be addressed provide insights perspectives turn into opportunities this field. Collectively, multiple emphasized review may guidance precision medicine, broaden horizons future research directions, expedite patients according their rather than organs origin.

Language: Английский

Citations

179
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

149
Altered metabolism in cancer: insights into energy pathways and therapeutic targets DOI Creative Commons
Muhammad Tufail, Canhua Jiang, Ning Li

et al.

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

Published: Sept. 18, 2024

Language: Английский

Citations

75
The Warburg effect: a score for many instruments in the concert of cancer and cancer niche cells DOI Creative Commons

Martyna Jaworska,

Julia Szczudło,

Adrian Pietrzyk

et al.

Pharmacological Reports, Journal Year: 2023, Volume and Issue: 75(4), P. 876 - 890

Published: June 19, 2023

Abstract Although Warburg's discovery of intensive glucose uptake by tumors, followed lactate fermentation in oxygen presence was made a century ago, it is still an area intense research and development new hypotheses that, layer layer, unravel the complexities neoplastic transformation. This seemingly simple metabolic reprogramming cancer cells reveals intriguing, multi-faceted nature that may link various phenomena including cell signaling, proliferation, ROS generation, energy supply, macromolecules synthesis/biosynthetic precursor immunosuppression, or cooperation cancerous with cancer-associated fibroblasts (CAFs), known as reversed Warburg effect. According to current perception causes consequences effect, PI3K/Akt/mTOR are main signaling pathways concert transcription factors HIF-1, p53, c-Myc, modulate activity/expression key regulatory enzymes, PKM2, PDK1 tune most optimal setting for cell. turn secures adequate levels biosynthetic precursors, NADPH, NAD + , rapid ATP production meet increased demands intensively proliferating tumor cells. The end-product “aerobic glycolysis”, lactate, oncometabolite, provide fuel neighboring cells, facilitate metastasis immunosuppression together enabling progression. importance possible applicability presented issue best illustrated numerous trials agents targeting constituting promising strategy future anti-cancer regimens. In this review, we present aspects multifactorial phenomenon, depicting mechanisms benefits behind also pointing selected field anticancer therapy.

Language: Английский

Citations

63
The role of glutamate and glutamine metabolism and related transporters in nerve cells DOI Creative Commons
Dongyang Zhang, Zhongyan Hua, Zhijie Li

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(2)

Published: Feb. 1, 2024

Glutamate and glutamine are the most abundant amino acids in blood play a crucial role cell survival nervous system. Various transporters found mitochondrial membranes, such as solute carriers (SLCs) superfamily, responsible for maintaining balance of glutamate synaptic cleft within cells. This affects metabolism non-essential acids.

Language: Английский

Citations

26
Hallmarks of cancer resistance DOI Creative Commons
Muhammad Tufail,

Jia-Ju Hu,

Jie Liang

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109979 - 109979

Published: May 15, 2024

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized Warburg effect, and dynamic interplay between cells mitochondria. The role stem (CSCs) in treatment resistance regulatory influence non-coding RNAs, such as long RNAs (lncRNAs), microRNAs (miRNAs), circular (circRNAs), are studied. chapter emphasizes future directions, encompassing advancements immunotherapy, strategies to counter adaptive integration artificial intelligence for predictive modeling, identification biomarkers personalized treatment. comprehensive exploration these provides a foundation innovative therapeutic approaches, aiming navigate complex landscape enhance patient outcomes.

Language: Английский

Citations

26
Crossing epigenetic frontiers: the intersection of novel histone modifications and diseases DOI Creative Commons

Weiyi Yao,

Xinting Hu,

Xin Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 16, 2024

Abstract Histone post-translational modifications (HPTMs), as one of the core mechanisms epigenetic regulation, are garnering increasing attention due to their close association with onset and progression diseases potential targeted therapeutic agents. Advances in high-throughput molecular tools abundance bioinformatics data have led discovery novel HPTMs which similarly affect gene expression, metabolism, chromatin structure. Furthermore, a growing body research has demonstrated that histone also play crucial roles development various diseases, including cancers, cardiovascular infectious psychiatric disorders, reproductive system diseases. This review defines nine modifications: lactylation, citrullination, crotonylation, succinylation, SUMOylation, propionylation, butyrylation, 2-hydroxyisobutyrylation, 2-hydroxybutyrylation. It comprehensively introduces modification processes these HPTMs, transcription, replication, DNA repair recombination, structure, well involvement promoting occurrence clinical applications targets biomarkers. Moreover, this provides detailed overview HPTM inhibitors targeting emerging strategies treatment multiple while offering insights into future prospects challenges. Additionally, we briefly introduce techniques field research.

Language: Английский

Citations

23
Activation of polyamine catabolism promotes glutamine metabolism and creates a targetable vulnerability in lung cancer DOI Creative Commons

Xinlu Han,

Deyu Wang, Yang Liao

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(13)

Published: March 21, 2024

Polyamines are a class of small polycationic alkylamines that play essential roles in both normal and cancer cell growth. Polyamine metabolism is frequently dysregulated considered therapeutic target cancer. However, targeting polyamine as monotherapy often exhibits limited efficacy, the underlying mechanisms incompletely understood. Here we report activation catabolism promotes glutamine metabolism, leading to targetable vulnerability lung Genetic pharmacological spermidine/spermine N1-acetyltransferase 1 (SAT1), rate-limiting enzyme catabolism, enhances conversion glutamate subsequent glutathione (GSH) synthesis. This metabolic rewiring ameliorates oxidative stress support proliferation survival. Simultaneous limitation SAT1 result ROS accumulation, growth inhibition, death. Importantly, inhibition either one transport, glutaminase, or GSH biosynthesis combination with synergistically suppresses xenograft tumor formation. Together, this study unveils previously unappreciated functional interconnection between establishes cotargeting strategies potential therapeutics

Language: Английский

Citations

18
Energy metabolism in health and diseases DOI Creative Commons
Hui Liu, Shuo Wang, Jianhua Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 18, 2025

Language: Английский

Citations

15