Cancer-associated fibroblasts: a versatile mediator in tumor progression, metastasis, and targeted therapy

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 43(3), P. 1095 - 1116

Published: April 11, 2024

Abstract Tumor microenvironment (TME) has been demonstrated to play a significant role in tumor initiation, progression, and metastasis. Cancer-associated fibroblasts (CAFs) are the major component of TME exhibit heterogeneous properties their communication with cells. This heterogeneity CAFs can be attributed various origins, including quiescent fibroblasts, mesenchymal stem cells (MSCs), adipocytes, pericytes, endothelial cells, mesothelial Moreover, single-cell RNA sequencing identified diverse phenotypes CAFs, myofibroblastic (myCAFs) inflammatory (iCAFs) being most acknowledged, alongside newly discovered subtypes like antigen-presenting (apCAFs). Due these heterogeneities, exert multiple functions tumorigenesis, cancer stemness, angiogenesis, immunosuppression, metabolism, As result, targeted therapies aimed at TME, particularly focusing on rapidly developing, fueling promising future advanced tumor-targeted therapy.

Language: Английский

---

Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: Oncometabolite fuels oncogenic transcription

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(3)

Published: March 1, 2024

Abstract Heightened lactate production in cancer cells has been linked to various cellular mechanisms such as angiogenesis, hypoxia, macrophage polarisation and T‐cell dysfunction. The lactate‐induced lactylation of histone lysine residues is noteworthy, it functions an epigenetic modification that directly augments gene transcription from chromatin. This originating effectively fosters a reliance on transcription, thereby expediting tumour progression development. Herein, this review explores the correlation between characteristics, revealing innovative process enhances vulnerability malignancy. Moreover, imperative acknowledge paramount importance acknowledging therapeutic methodologies for proficiently managing by precisely targeting signalling. comprehensive illuminates crucial yet inadequately investigated aspect lactylation, providing valuable insights into its clinical ramifications prospective interventions centred lactylation.

Language: Английский

---

Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer

Cellular & Molecular Biology Letters, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 6, 2025

Abstract Hypoxia-inducible factors (HIFs) are essential transcription that orchestrate cellular responses to oxygen deprivation. HIF-1α, as an unstable subunit of HIF-1, is usually hydroxylated by prolyl hydroxylase domain enzymes under normoxic conditions, leading ubiquitination and proteasomal degradation, thereby keeping low levels. Instead hypoxia, sometimes even in normoxia, HIF-1α translocates into the nucleus, dimerizes with HIF-1β generate then activates genes involved adaptive such angiogenesis, metabolic reprogramming, survival, which presents new challenges insights its role processes. Thus, review delves mechanisms HIF-1 maintains stability normoxia including but not limited giving transcriptional, translational, well posttranslational regulation underscore pivotal adaptation malignancy. Moreover, extensively cancer cardiovascular diseases potentially serves a bridge between them. An overview HIF-1-related drugs approved or clinical trials summarized, highlighting their potential capacity for targeting toxicity related treatment. The provides comprehensive insight HIF-1’s regulatory mechanism paves way future research therapeutic development.

Language: Английский

---

The immune checkpoint TIGIT/CD155 promotes the exhaustion of CD8 + T cells in TNBC through glucose metabolic reprogramming mediated by PI3K/AKT/mTOR signaling

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

Published: Jan. 12, 2024

Abstract Objective The CD155/TIGIT axis has attracted considerable interest as an emerging immune checkpoint with potential applications in cancer immunotherapy. Our research focused on investigating the role of checkpoints progression triple-negative breast (TNBC). Methods We evaluated CD155 and TIGIT expression TNBC tissues using both immunohistochemistry (IHC) gene profiling. experiments, vivo vitro, provided evidence that inhibiting pathway reinstates ability CD8 + T cells to generate cytokines. To assess impact signaling blockade, we utilized Glucose Assay Kits Lactate measure alterations glucose lactate levels within cells. employed western blotting (WB) investigate glycolytic-related proteins PI3K/AKT/mTOR pathways following inhibition signaling. Results exhibits heightened a negative correlation extent infiltrating Furthermore, patients demonstrate elevated expression. findings indicate interaction between disrupts metabolism by suppressing activation pathway, ultimately leading reduced production cytokines Both vitro experiments have conclusively demonstrated capacity Moreover, administration blocking antibody against not only inhibits tumor growth but also augments functionality lymphocytes. Conclusions strongly suggest represents promising therapeutic target for treating TNBC.

Language: Английский

---

The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(3)

Published: March 13, 2024

Altered metabolism represents a fundamental difference between cancer cells and normal cells. Cancer have unique ability to reprogram their by deviating reliance from primarily oxidative phosphorylation (OXPHOS) glycolysis, in order support survival. This metabolic phenotype is referred as the “Warburg effect” associated with an increase glucose uptake, diversion of glycolytic intermediates alternative pathways that anabolic processes. These processes include synthesis nucleic acids, lipids, proteins, necessary for rapidly dividing cells, sustaining growth, proliferation, capacity successful metastasis. Triple-negative breast (TNBC) one most aggressive subtypes cancer, poorest patient outcome due its high rate TNBC characterized elevated glycolysis certain instances, low OXPHOS. dysregulation linked chemotherapeutic resistance research models samples. There more than single mechanism which this switch occurs here, we review current knowledge relevant molecular mechanisms involved advanced metabolism, focusing on TNBC. Warburg effect, adaptations, microRNA regulation, mitochondrial involvement, calcium signaling, recent player JAK/STAT signaling. In addition, explore some drugs compounds targeting reprogramming. Research these highly promising could ultimately offer new opportunities development innovative therapies treat dysregulated metabolism.

Language: Английский

---

Transcriptional regulation and post-translational modifications in the glycolytic pathway for targeted cancer therapy

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: 45(8), P. 1533 - 1555

Published: April 15, 2024

Language: Английский

---

The molecular code of kidney cancer: A path of discovery for gene mutation and precision therapy

Molecular Aspects of Medicine, Journal Year: 2025, Volume and Issue: 101, P. 101335 - 101335

Published: Jan. 1, 2025

Renal cell carcinoma (RCC) is a malignant tumor with highly heterogeneous and complex molecular mechanisms. Through systematic analysis of TCGA, COSMIC other databases, 24 mutated genes closely related to RCC were screened, including VHL, PBRM1, BAP1 SETD2, which play key roles in signaling pathway transduction, chromatin remodeling DNA repair. The PI3K/AKT/mTOR particularly important the pathogenesis RCC. Mutations such as PIK3CA, MTOR PTEN are associated metabolic abnormalities proliferation. Clinically, mTOR inhibitors VEGF-targeted drugs have shown significant efficacy personalized therapy. Abnormal regulation reprogramming, especially glycolysis glutamine pathways, provides cells continuous energy supply survival advantages, GLS1 promising results preclinical studies. This paper also explores potential immune checkpoint combination targeted drugs, well application nanotechnology drug delivery In addition, unique mechanisms revealed individualized therapeutic strategies explored for specific subtypes TFE3, TFEB rearrangement type SDHB mutant type. review summarizes common gene mutations their mechanisms, emphasizes diagnosis, treatment prognosis, looks forward prospects multi-pathway therapy, immunotherapy treatment, providing theoretical support clinical guidance new development.

Language: Английский

---

A novel silkworm excrement-derived nanomedicine integrating ferroptosis and photodynamic therapy, well-suitable for PD-L1-mediated immune checkpoint blockade

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: 505, P. 159676 - 159676

Published: Jan. 17, 2025

Language: Английский

---

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

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

---

Targeting hypoxic and acidic tumor microenvironment by nanoparticles: A review

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 96, P. 105660 - 105660

Published: April 12, 2024

Language: Английский

---