Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies DOI Creative Commons
Giulia Ambrosini, Marco Cordani, Ali Zarrabi

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 12, 2024

Abstract Prostate cancer, as one of the most prevalent malignancies in males, exhibits an approximate 5-year survival rate 95% advanced stages. A myriad molecular events and mutations, including accumulation oncometabolites, underpin genesis progression this cancer type. Despite growing research demonstrating pivotal role oncometabolites supporting various cancers, prostate root causes their accumulation, especially absence enzymatic remain elusive. Consequently, identifying a tangible therapeutic target poses formidable challenge. In review, we aim to delve deeper into implications oncometabolite cancer. We center our focus on consequential epigenetic alterations impacts stem cells, with ultimate goal outlining novel strategies. Graphical

Language: Английский

Metabolic programming and immune suppression in the tumor microenvironment DOI Creative Commons
Emily N. Arner, Jeffrey C. Rathmell

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 421 - 433

Published: Feb. 16, 2023

Language: Английский

Citations

258
Embracing cancer complexity: Hallmarks of systemic disease DOI Open Access
Charles Swanton, Elsa Bernard,

Chris Abbosh

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(7), P. 1589 - 1616

Published: March 1, 2024

Language: Английский

Citations

161
Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy DOI Open Access
Miljana Nenkov, Yunxia Ma,

Nikolaus Gaßler

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(12), P. 6262 - 6262

Published: June 10, 2021

Colorectal carcinoma (CRC) is one of the most frequently diagnosed carcinomas and leading causes cancer-related death worldwide. Metabolic reprogramming, a hallmark cancer, closely related to initiation progression carcinomas, including CRC. Accumulating evidence shows that activation oncogenic pathways loss tumor suppressor genes regulate metabolic reprogramming mainly involved in glycolysis, glutaminolysis, one-carbon metabolism lipid metabolism. The abnormal program provides cells with abundant energy, nutrients redox requirements support their malignant growth metastasis, which accompanied by impaired flexibility microenvironment (TME) dysbiosis gut microbiota. crosstalk between cells, components TME intestinal microbiota further facilitates CRC cell proliferation, invasion metastasis leads therapy resistance. Hence, target dysregulated metabolism, microbiota, novel preventive therapeutic applications are required. In this review, dysregulation programs, molecular pathways, addressed. Possible strategies, inhibition immune CRC, as well modulation aberrant discussed.

Language: Английский

Citations

106
Amplification of spatially isolated adenosine pathway by tumor–macrophage interaction induces anti-PD1 resistance in hepatocellular carcinoma DOI Creative Commons

Jia‐Cheng Lu,

Pengfei Zhang, Xiaoyong Huang

et al.

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Nov. 27, 2021

Abstract Background Immune checkpoint blockade resistance narrows the efficacy of cancer immunotherapies, but underlying mechanism remains elusive. Delineating inherent mechanisms anti-PD1 is important to improve outcome patients with advanced HCC. Method The level cricTMEM181 was measured in HCC therapy by RNA sequencing and then confirmed qPCR Sanger sequencing. status tumor microenvironment or mice models evaluated flow cytometry IHC. Exosomes from cell lines were isolated ultracentrifugation, their internalization macrophage immunofluorescence. HCC-derived exosomal circTMEM181 SILAC, FISH immunoprecipitation. ATP–ADO pathway amplified HCC–macrophage interaction through ATP, AMP ADO measurement macrophage-specific CD39 knockout mice. role its clinical significance also determined our retrospective cohorts. Results Here, we found that elevated hepatocellular carcinoma (HCC) responding poorly a poor prognosis after operation. Moreover, high favored immunosuppressive endowed Mechanistically, sponged miR-488-3p upregulated expression macrophages. Using pharmacologic approaches, revealed novel mode We discovered cell-specific macrophages CD73 cells synergistically activated eATP–adenosine produced more adenosine, thereby impairing CD8 + T function driving resistance. Conclusion In summary, contributes immunosuppression elevating expression, inhibiting ATP–adenosine targeting on can rescue Graphical

Language: Английский

Citations

106
Metabolic reprogramming in cholangiocarcinoma DOI
Chiara Raggi, Maria Letizia Taddei, Colin Rae

et al.

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 77(3), P. 849 - 864

Published: May 18, 2022

Language: Английский

Citations

99
Metabolic challenges and interventions in CAR T cell therapy DOI
Jhan-Jie Peng, Limei Wang, Zhiyu Li

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(82)

Published: April 14, 2023

Chimeric antigen receptor (CAR) T cells have achieved true clinical success in treating hematological malignancy patients, laying the foundation of CAR as a new pillar cancer therapy. Although these promising effects generated strong interest expanding treatment to solid tumors, reproducible demonstration efficacy setting tumors has remained challenging date. Here, we review how metabolic stress and signaling tumor microenvironment, including intrinsic determinants response cell therapy extrinsic obstacles, restrict treatment. In addition, discuss use novel approaches target rewire programming for manufacturing. Last, summarize strategies that aim improve adaptability enhance their potency mounting antitumor responses survival within microenvironment.

Language: Английский

Citations

59
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

58
Beggars banquet: Metabolism in the tumor immune microenvironment and cancer therapy DOI Creative Commons
Weiping Zou, Douglas R. Green

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(7), P. 1101 - 1113

Published: June 29, 2023

Language: Английский

Citations

48
Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF-𝜅B-IL-6 axis of tumor-associated macrophages DOI Creative Commons
Boxuan Zhou,

Zhaohong Mo,

Guie Lai

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Feb. 17, 2023

Circular RNAs (circRNAs) have important regulatory functions in cancer, but the role of circRNAs tumor microenvironment (TME) remains unclear. Moreover, we also explore effects si-circRNAs loaded nanoparticles as therapeutic agent for anti-tumor vivo.We conducted bioinformatics analysis, qRT-PCR, EdU assays, Transwell co-culture system and multiple orthotopic xenograft models to investigate expression function circRNAs. Additionally, PLGA-based with were used evaluate potential nanotherapeutic strategy response.We identified oncogene SERPINE2 derived circRNA, named cSERPINE2, which was notably elevated breast cancer closely related poor clinical outcome. Functionally, exosomal cSERPINE2 shuttled associated macrophages (TAMs) enhanced secretion Interleukin-6 (IL-6), leading increased proliferation invasion cells. Furthermore, IL-6 turn EIF4A3 CCL2 levels within cells a positive feedback mechanism, further enhancing biogenesis promoting recruitment TAMs. More importantly, developed nanoparticle si-cSERPINE2, effectively attenuated progression vivo.Our study illustrates novel mechanism that mediates loop between TAMs promote progression, may serve promising treatment cancer.

Language: Английский

Citations

46
Pancreatic tumors exhibit myeloid-driven amino acid stress and upregulate arginine biosynthesis DOI Creative Commons
Juan J Apiz Saab, Lindsey N. Dzierozynski, Patrick B. Jonker

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 31, 2023

Nutrient stress in the tumor microenvironment requires cancer cells to adopt adaptive metabolic programs for survival and proliferation. Therefore, knowledge of microenvironmental nutrient levels how cope with such nutrition is critical understand metabolism underpinning cell biology. Previously, we performed quantitative metabolomics interstitial fluid (the local perfusate) murine pancreatic ductal adenocarcinoma (PDAC) tumors comprehensively characterize availability these tumors. Here, develop

Language: Английский

Citations

44