Tumor metabolic regulators: key drivers of metabolic reprogramming and the promising targets in cancer therapy

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Янв. 9, 2025

Metabolic reprogramming within the tumor microenvironment (TME) is a hallmark of cancer and crucial determinant progression. Research indicates that various metabolic regulators form network in TME interact with immune cells, coordinating response. dysregulation creates an immunosuppressive TME, impairing antitumor In this review, we discuss how affect cell crosstalk TME. We also summarize recent clinical trials involving challenges metabolism-based therapies translation. word, our review distills key regulatory factors their mechanisms action from complex metabolism, identified as regulators. These provide theoretical basis research direction for development new strategies targets therapy based on reprogramming. Refining Depicting between stromal cells during Emphasizing unresolved translation advantages personalized treatment. Providing support therapies.

Язык: Английский

---

Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Март 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Язык: Английский

---

Arenobufagin suppresses the progression of early-stage hepatocellular carcinoma by inhibiting EpCAM-mediated tumor stemness

Acta Materia Medica, Год журнала: 2025, Номер 4(1)

Опубликована: Янв. 1, 2025

Epithelial cell adhesion molecule (EpCAM) is a biomarker for epithelial cell-derived tumors. However, the specific role of EpCAM itself in early-stage hepatocellular carcinoma progression remains unclear, and small molecules targeting have not yet been reported. Here, protein expression profile tumor-adjacent regions was found to be higher than that tumor regions, positively associated with liver cancer, as well high frequency recurrence, cirrhosis, lymph node metastasis, microvascular invasion cancer stemness, 68 patients (HCC). In vitro , enhanced reflected by increased abilities proliferation, self-renewal, migration invasion, which counteracted arenobufagin. Furthermore, arenobufagin inhibited viability Hep3B Huh7 cells IC 50 values 36.4 nM 123.4 after 72 h treatment, respectively. Molecular docking data further indicated binds EpCAM. Moreover, early HCC through zebrafish xenograft model mimicking without blood vessels vivo . This study supports tumor-promoting facilitating stemness suggests might promising candidate inhibition.

Язык: Английский

---

The Role of Cholesterol Metabolism and Its Regulation in Tumor Development

Cancer Medicine, Год журнала: 2025, Номер 14(7)

Опубликована: Март 27, 2025

ABSTRACT Background Within the tumor microenvironment, cells undergo metabolic reprogramming of cholesterol due to intrinsic cellular alterations and changes in extracellular milieu. Furthermore, within this microenvironment influences immune landscape tumors, facilitating evasion consequently promoting tumorigenesis. These biological involve modifications numerous enzymes associated with uptake synthesis, including NPC1L1, SREBP, HMGCR, SQLE, PCSK9. Review This review systematically summarizes role metabolism its cancer progression, examines mechanisms through which dysregulation affects discusses recent advancements therapies that target metabolism. Conclusion Targeting metabolism‐related can inhibit growth, reshape landscapes, rejuvenate antitumor immunity, offering potential therapeutic avenues treatment.

Язык: Английский

---

Cholesterol effects on the tumor immune microenvironment: from fundamental concepts to mechanisms and implications

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Апрель 9, 2025

In many cancers, the tumor microenvironment is enriched with cholesterol due to increased biosynthesis and uptake by cancer cells, resulting in accumulation of cholesterol, esters, oxysterols other metabolites various functions. These molecules serve as structural components, energy sources intracellular signaling mediators, while their toxic by-products are secreted suppress anti-tumor immune activity prevent lipid peroxidation that could induce cell apoptosis. Immune cells also contribute dynamics. Tumor-associated macrophages (TAMs) release support metabolism, myeloid-derived suppressor (MDSCs) consume essential such L-arginine, which impairs T-cell proliferation activation. Elevated dendritic migration antigen presentation and, lymphocytes, favors development a regulatory T (Treg) phenotype inhibits antitumor cytokines, further weakening response. findings suggest targeting metabolism promising strategy for treatment, improving efficacy checkpoint blockade (ICB) therapies. this manuscript, molecular mechanisms underlying effects on landscape reviewed potential cholesterol-lowering drugs enhance responses explored.

Язык: Английский

---

Unveiling the contribution of tumor-associated macrophages in driving epithelial-mesenchymal transition: a review of mechanisms and therapeutic Strategies

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Сен. 2, 2024

Tumor-associated macrophages (TAMs), fundamental constituents of the tumor microenvironment (TME), significantly influence cancer development, primarily by promoting epithelial-mesenchymal transition (EMT). EMT endows cells with increased motility, invasiveness, and resistance to therapies, marking a pivotal juncture in progression. The review begins detailed exposition on origins TAMs their functional heterogeneity, providing foundational understanding TAM characteristics. Next, it delves into specific molecular mechanisms through which induce EMT, including cytokines, chemokines stromal cross-talking. Following this, explores TAM-induced features select types notable characteristics, highlighting recent insights impact Finally, concludes discussion potential therapeutic targets strategies aimed at mitigating infiltration disrupting signaling network, thereby underscoring emerging treatments combat TAM-mediated cancer. This comprehensive analysis reaffirms necessity for continued exploration TAMs’ regulatory roles within biology refine approaches improve patient outcomes.

Язык: Английский

---

Activated PARP1/FAK/COL5A1 signaling facilitates the tumorigenesis of cholesterol-resistant ovarian cancer cells through promoting EMT

Cellular Signalling, Год журнала: 2024, Номер 124, С. 111419 - 111419

Опубликована: Сен. 16, 2024

Язык: Английский

---