Editorial: Metabolic reprogramming in cancer DOI Creative Commons
Valentina Audrito, Elisa Giovannetti

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 11, 2025

In their review article Chen et al. summarized the main features of metabolic reprogramming in tumors, addressing different aspects including increased glycolytic metabolism, lipid synthesis, alteration amino acids production, and relationship between altered metabolism immune response. Then, they focused paper on roles played by adaptation mechanisms prognosis progression kidney cancer, discussing recent advancements diagnosis treatment renal cancer targeting vulnerabilities. The role was also emphasized systematic Li analyzing hepatocellular carcinoma (HCC), a with high morbidity mortality. authors selected from 2011 to 2023 total 575 publications this field identify hotspots frontiers research HCC provide future directions for novel scientific decision-making therapeutic strategies. context rewiring serine hydroxymethyltransferases (SHMTs) methylenetetrahydrofolate dehydrogenases (MTHFDs) are recognized as important one-carbon enzymes regulating tumor initiation development, representing potential targets anti-tumor strategies, illustrated Zhang MTHFD1/2 have been identified oncogenic upregulated various involved metastasis formation chemoresistance. Cytoplasmic SHMT1 mitochondrial SHMT2 units nucleotide biosynthesis, DNA methylation NADPH generation, during development. Wang discuss how esophageal squamous cell (ESCC) cells adapt hypoxic, nutrient-deprived microenvironment glucose, lipid, acid metabolism. This shift ensures survival proliferation despite adverse conditions, highlighting new avenues intervention. study identifies vulnerabilities ESCC, suggesting that disrupting these adaptive pathways could improve efficacy. Xie further explore hypoxia-related genes influence immunotherapeutic outcomes ESCC. They establish an HPRscore based hypoxia phenotype-related genes, demonstrating its predictive power patient response treatment. Notably, PKP1 target, showing knockdown reduces migration. These findings valuable insight into hypoxia-driven changes affect behavior evasion. Peppicelli melanoma resistant anoikis, investigate within circulating (CTCs), aim identifying CTCs. discovered anoikis-resistant suspension show characteristic pathway toward more oxidative use glutamine fatty acids, while re-adhesion CTCs dishes reversed glycolysis. inhibition switch led reduction viability colony ability capable surviving suspension, offering strategies metastases. Similar adaptations evident colorectal (CRC), where evasion is closely tied shifts microenvironment. Nicolini examine CRC undergo reprogramming-from enhanced glycolysis synthesis-to create immunosuppressive lactate acidification, driven Warburg effect, impairs promotes tumor-associated macrophages (TAMs) regulatory T (Tregs). explores genetic mutations (e.g., RAS, EGFR) microbiota shaping emphasizing metabolic-targeted therapies combination checkpoint inhibitors (ICIs). Gao broader perspective key tool precision medicine. highlight types rely distinct adaptations, necessitating tailored approaches. underscores growing importance profiling developing personalized treatments, optimizing responses, overcoming drug resistance. Ferroptosis, non-apoptotic form death iron-dependent peroxidation, plays paradoxical cancer. Complex ferroptosis. As explored Zhao ferroptosis can both suppress promote growth depending cellular mechanisms. highlights enhancing sensitivity resistance Understanding critical particularly immunotherapies interventions. Of note, one driver which vital stem (CSC) maintenance. Du CSCs manipulate sustain stemness, resist therapy, environmental stress. describe increase content energy, engage β-oxidation optimize utilization, enhance cholesterol synthesis through mevalonate pathway. Additionally, droplets serve alternative energy reservoirs, protecting need target weaken CSC resilience outcomes. Lastly, Ping original using retrospective analysis described value plasma omega-3 polyunsaturated (omega-3 PUFAs) levels early response, free survival, overall patients cervical (CSCC) who underwent concurrent chemoradiotherapy (CCRT). Interestingly, demonstrated pretreatment PUFAs level, may be promising biomarker predicting CSCC, increasing prognostic significance serum antigen (SCC)-Ag level alone, opening tools clinicians CSCC.Together, studies reveal drives progression, contributes chemoresistance, interconnected Targeting holds great promise improving treatment, immunotherapy medicine

Language: Английский

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

148
Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma DOI Creative Commons
Fei Li, Wenzhe Si,

Li Xia

et al.

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

Published: May 6, 2024

Abstract Background Metabolic reprogramming and epigenetic alterations contribute to the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). Lactate-dependent histone modification is a new type mark, which links glycolysis metabolite process lactylation. However, role lactylation in PDAC remains unclear. Methods The level was identified by western blot immunohistochemistry, its relationship with overall survival evaluated using Kaplan-Meier plot. participation growth progression confirmed through inhibition inhibitors or lactate dehydrogenase A ( LDHA ) knockdown both vitro vivo. potential writers erasers were functional experiments. target genes H3K18 (H3K18la) screened CUT&Tag RNA-seq analyses. candidate TTK protein kinase BUB1 mitotic checkpoint serine/threonine B BUB1B validated ChIP-qPCR, RT-qPCR Next, effects these two overexpression. interaction between Co-IP assay. Results Histone lactylation, especially H3K18la elevated PDAC, high associated poor prognosis. suppression glycolytic activity different kinds contributed anti-tumor E1A binding p300 (P300) deacetylase 2 writer eraser cells, respectively. enriched at promoters activated transcription regulators . Interestingly, could elevate expression P300 turn increased glycolysis. Moreover, phosphorylated tyrosine 239 (Y239) LDHA, subsequently upregulated levels. Conclusions glycolysis-H3K18la-TTK/BUB1B positive feedback loop exacerbates dysfunction PDAC. These findings delivered exploration significant inter-relationship metabolic regulation, might pave way toward novel treatment strategies therapy.

Language: Английский

Citations

52
The emerging role of lactate in tumor microenvironment and its clinical relevance DOI

Sihan Chen,

Yining Xu,

Wei Zhuo

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 590, P. 216837 - 216837

Published: March 26, 2024

Language: Английский

Citations

30
Lactate and lactylation in cancer DOI Creative Commons
Jie Chen, Ziyue Huang,

Ya Chen

et al.

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

Published: Feb. 11, 2025

Abstract Accumulated evidence has implicated the diverse and substantial influence of lactate on cellular differentiation fate regulation in physiological pathological settings, particularly intricate conditions such as cancer. Specifically, been demonstrated to be pivotal molding tumor microenvironment (TME) through its effects different cell populations. Within cells, impacts signaling pathways, augments shuttle process, boosts resistance oxidative stress, contributes lactylation. In various populations, interplay between immune cells governs processes differentiation, response, surveillance, treatment effectiveness. Furthermore, communication stromal/endothelial supports basal membrane (BM) remodeling, epithelial-mesenchymal transitions (EMT), metabolic reprogramming, angiogenesis, drug resistance. Focusing production transport, specifically dehydrogenase (LDH) monocarboxylate transporters (MCT), shown promise Inhibitors targeting LDH MCT act both suppressors enhancers immunotherapy, leading a synergistic therapeutic effect when combined with immunotherapy. The review underscores importance progression provides valuable perspectives potential approaches that target vulnerability metabolism, highlighting Heel Achilles for cancer treatment.

Language: Английский

Citations

9
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

8
The role of metabolic reprogramming in pancreatic cancer chemoresistance DOI Creative Commons
Chang Liu, Changfeng Li,

Yuanda Liu

et al.

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

Published: Jan. 9, 2023

Pancreatic cancer is characterized by hidden onset, high malignancy, and early metastasis. Although a few cases meet the surgical indications, chemotherapy remains primary treatment, resulting chemoresistance has become an urgent clinical problem that needs to be solved. In recent years, importance of metabolic reprogramming as one hallmarks cancers in tumorigenesis been validated. Metabolic involves glucose, lipid, amino acid metabolism interacts with oncogenes affect expression key enzymes signaling pathways, modifying tumor microenvironment contributing occurrence drug tolerance. Meanwhile, mitochondria are hubs three major nutrients energy metabolisms, which also involved development resistance. this review, we summarized characteristic changes during progression pancreatic their impact on chemoresistance, outlined role mitochondria, current studies inhibitors.

Language: Английский

Citations

23
Regulation of newly identified lysine lactylation in cancer DOI
Xin Gao,

Chaoyu Pang,

Zhiyao Fan

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 587, P. 216680 - 216680

Published: Feb. 10, 2024

Language: Английский

Citations

15
Advances in metabolic reprogramming of NK cells in the tumor microenvironment on the impact of NK therapy DOI Creative Commons

Linxuan Miao,

Chenglin Lu, Bin Zhang

et al.

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

Published: March 3, 2024

Abstract Natural killer (NK) cells are unique from other immune in that they can rapidly kill multiple neighboring without the need for antigenic pre-sensitization once display surface markers associated with oncogenic transformation. Given dynamic role of NK tumor surveillance, cell-based immunotherapy is becoming a "new force" immunotherapy. However, challenges remain use cell treatment solid tumors. Many metabolic features microenvironment (TME) tumors, including oxygen and nutrient (e.g., glucose, amino acids) deprivation, accumulation specific metabolites lactate, adenosine), limited availability signaling molecules allow reorganization, multifactorial shaping immune-suppressing TME impairs tumor-infiltrating function. This becomes key barrier limiting success Restoration endogenous or overt transfer functionally improved holds great promise cancer therapy. In this paper, we summarize biology cells, discuss effects on metabolism effector functions, review emerging strategies targeting metabolism-improved to circumvent these barriers achieve superior efficacy

Language: Английский

Citations

14
Emerging Trends in Gastrointestinal Cancer Targeted Therapies: Harnessing Tumor Microenvironment, Immune Factors, and Metabolomics Insights DOI
Sanchita Rauth, Mokenge P. Malafa, Moorthy P. Ponnusamy

et al.

Gastroenterology, Journal Year: 2024, Volume and Issue: 167(5), P. 867 - 884

Published: May 15, 2024

Language: Английский

Citations

13
Emerging mechanisms and promising approaches in pancreatic cancer metabolism DOI Creative Commons
Hao Wu,

Mengdi Fu,

Mengwei Wu

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)

Published: Aug. 1, 2024

Abstract Pancreatic cancer is an aggressive with a poor prognosis. Metabolic abnormalities are one of the hallmarks pancreatic cancer, and cells can adapt to biosynthesis, energy intake, redox needs through metabolic reprogramming tolerate nutrient deficiency hypoxic microenvironments. use glucose, amino acids, lipids as maintain malignant growth. Moreover, they also metabolically interact in tumour microenvironment change cell fate, promote progression, even affect immune responses. Importantly, changes at body level deserve more attention. Basic research clinical trials based on targeted therapy or combination other treatments full swing. A comprehensive in-depth understanding regulation will not only enrich mechanisms disease progression but provide inspiration for new diagnostic therapeutic approaches.

Language: Английский

Citations

13