The Basis for Targeting the Tumor Macrophage Compartment in Glioblastoma Immunotherapy DOI Open Access

Thomas Eckert,

Chase M. Walton, Marcus Bell

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(10), P. 1631 - 1631

Published: May 12, 2025

Background: Glioblastoma (GBM) remains the most aggressive primary brain tumor with limited treatment options. The immunosuppressive microenvironment (TME), largely shaped by tumor-associated macrophages (TAMs), represents a significant barrier to effective immunotherapy. Objective: This review aims explore role of TAMs within TME, highlighting phenotypic plasticity, interactions cells, and potential therapeutic targets enhance anti-tumor immunity. Findings: constitute substantial portion displaying functional plasticity between pro-inflammatory phenotypes. Strategies targeting include depletion, reprogramming, inhibition pro-tumor signaling pathways. Preclinical studies show that modifying TAM behavior can shift TME towards state, enhancing antitumor immune responses. Clinical trials investigating inhibitors recruitment, polarization, downstream pathways reveal promising yet results, necessitating further research optimize approaches. Conclusions: Therapeutic strategics through selective or modulation signals represent avenues overcome GBM-associated immunosuppression. Early clinical underscore their safety feasibility, achieving meaningful efficacy requires deeper mechanistic understanding combinatorial approaches integrating macrophage-direct therapies existing immunotherapeutic modalities.

Language: Английский

Drug repurposing for cancer therapy DOI Creative Commons
Ying Xia, Ming Sun, Hai Huang

et al.

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

Published: April 18, 2024

Abstract Cancer, a complex and multifactorial disease, presents significant challenge to global health. Despite advances in surgical, radiotherapeutic immunological approaches, which have improved cancer treatment outcomes, drug therapy continues serve as key therapeutic strategy. However, the clinical efficacy of is often constrained by resistance severe toxic side effects, thus there remains critical need develop novel therapeutics. One promising strategy that has received widespread attention recent years repurposing: identification new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages context since repurposed drugs are typically cost-effective, proven be safe, can significantly expedite development process due their already established safety profiles. In light this, present review offers comprehensive overview various methods employed repurposing, specifically focusing on treat cancer. We describe antitumor properties candidate drugs, discuss detail how they target both hallmarks tumor cells surrounding microenvironment. addition, we examine innovative integrating with nanotechnology enhance topical delivery. also emphasize role play when used part combination regimen. To conclude, outline challenges associated consider future prospects these transitioning into application.

Language: Английский

Citations

110
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

71
Targeting lipid metabolism: novel insights and therapeutic advances in pancreatic cancer treatment DOI Creative Commons
Yanyan Zhang, Zhichao Yang, Yuchen Liu

et al.

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 13, 2025

Lipid metabolism in cancer is characterized by dysregulated lipid regulation and utilization, critical for promoting tumor growth, survival, resistance to therapy. Pancreatic (PC) a highly aggressive malignancy of the gastrointestinal tract that has dismal 5-year survival rate less than 10%. Given essential function pancreas digestion, progression severely disrupts its function. Standard treatments PC such as surgical resection, chemotherapy, radiotherapy. However, these therapies often face significant challenges, including biochemical recurrence drug resistance. limitations, new therapeutic approaches are being developed target metabolism. Dysregulation cholesterol biosynthesis alterations fatty acids (FAs), palmitate, stearate, omega-3, omega-6, have been observed pancreatic cancer. These lipids serve energy sources, signaling molecules, components cell membranes. Their accumulation fosters an immunosuppressive microenvironment supports proliferation metastasis. Moreover, dysregulation within immune cells, particularly T impairs surveillance weakens body's defenses against Abnormal also contributes PC. Despite targeting may offer promising strategy. By enhancing peroxidation, induction ferroptosis—a form regulated death—could impair cells hinder disease progression.

Language: Английский

Citations

2
New insights into the therapeutic potentials of statins in cancer DOI Creative Commons
Chengyu Liu, Hong Chen, Bicheng Hu

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: July 7, 2023

The widespread clinical use of statins has contributed to significant reductions cardiovascular morbidity and mortality. Increasing preclinical epidemiological evidences have revealed that dyslipidemia is an important risk factor for carcinogenesis, invasion metastasis, as powerful inhibitor HMG-CoA reductase can exert prevention intervention effects on cancers, promote sensitivity anti-cancer drugs. mechanisms include not only inhibition cholesterol biosynthesis, but also their pleiotropic in modulating angiogenesis, apoptosis, autophagy, tumor microenvironment. Moreover, recent studies provided growing insights into the therapeutic potentials feasibility combining with other agents. Here, we provide updated review application potential cancer treatment summarize underneath mechanisms, focuses data from studies.

Language: Английский

Citations

30
Lipid metabolism and its implications in tumor cell plasticity and drug resistance: what we learned thus far? DOI Creative Commons
Ravichandran Vishwa, Bandari BharathwajChetty, Sosmitha Girisa

et al.

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 43(1), P. 293 - 319

Published: March 1, 2024

Metabolic reprogramming, a hallmark of cancer, allows cancer cells to adapt their specific energy needs. The Warburg effect benefits in both hypoxic and normoxic conditions is well-studied reprogramming metabolism cancer. Interestingly, the alteration other metabolic pathways, especially lipid has also grabbed attention scientists worldwide. Lipids, primarily consisting fatty acids, phospholipids cholesterol, play essential roles as structural component cell membrane, signalling molecule reserves. This involves aberrations uptake, synthesis breakdown lipids, thereby contributing survival, proliferation, invasion, migration metastasis cells. development resistance existing treatment modalities poses major challenge field therapy. Also, plasticity tumor was reported be factor for resistance. A number studies implicated that dysregulated contributes associated drug Therefore, it important understand intricate In this review, we mainly focused on implication disturbed events inducing plasticity-mediated addition, discussed concept peroxidation its crucial role phenotypic switching ferroptosis Elucidating relationship between metabolism, emergence will open new opportunities develop innovative strategies combinatorial approaches

Language: Английский

Citations

15
Mechanistic studies of tumor-associated macrophage immunotherapy DOI Creative Commons

Jiandong Cao,

Chengsen Liu

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 30, 2024

Tumor-associated macrophages (TAMs) are present in the tumor microenvironment and can polarize into subtypes with different functions characteristics response to stimuli, classifying them anti-tumorigenic M1-type pro-tumorigenic M2-type. The inhibit growth through release of pro-inflammatory cytokines, whereas M2-type contribute progression promotion proliferation, angiogenesis metastasis. Due duality macrophage effects on tumors, TAMs have been a hot topic research. In this paper, heterogeneity plasticity TAMs, interactions between other immune cells, tumors reviewed, therapeutic strategies for summarized discussed. These encompass methods approaches recruitment deplete modulate polarization TAMs. studies help deeply understand mechanism TAMs-tumor interaction provide reference combination therapy tumors.

Language: Английский

Citations

9
Metabolic crossroads: unravelling immune cell dynamics in gastrointestinal cancer drug resistance DOI Open Access

C. Raman Suri,

Babita Pande,

Lakkakula Suhasini Sahithi

et al.

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Metabolic reprogramming within the tumor microenvironment (TME) plays a critical role in driving drug resistance gastrointestinal cancers (GI), particularly through pathways of fatty acid oxidation and glycolysis. Cancer cells often rewire their metabolism to sustain growth reshape TME, creating conditions such as nutrient depletion, hypoxia, acidity that impair antitumor immune responses. Immune TME also undergo metabolic alterations, frequently adopting immunosuppressive phenotypes promote progression reduce efficacy therapies. The competition for essential nutrients, glucose, between cancer compromises functions effector cells, T cells. Additionally, by-products like lactate kynurenine further suppress activity populations, including regulatory M2 macrophages. Targeting glycolysis presents new opportunities overcome improve therapeutic outcomes GI cancers. Modulating these key has potential reinvigorate exhausted shift toward phenotypes, enhance effectiveness immunotherapies other treatments. Future strategies will require continued research into metabolism, development novel inhibitors, clinical trials evaluating combination Identifying validating biomarkers be crucial patient stratification treatment monitoring. Insights may have broader implications across multiple types, offering avenues improving treatment.

Language: Английский

Citations

1
Dysregulation of cholesterol homeostasis in cancer pathogenesis DOI Creative Commons
Aleksandra Mordzińska-Rak, Grégory Verdeil, Yannick Hamon

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: April 21, 2025

Cholesterol is a unique lipid for all mammalian cells, with important functions in membrane biogenesis and maintenance of proper integrity fluidity. Therefore, it plays an role cellular homeostasis. Dysregulation cholesterol homeostasis associated various diseases humans, including cardiovascular diseases, inflammatory neurodegenerative disorders, cancers. In the tumor microenvironment, intrinsic extrinsic factors reprogram metabolism consequently promote tumorigenesis. Here, we summarize current knowledge on molecular mechanisms functional roles its dysregulation regard to cancer pathogenesis. We also discuss interplay ATP-binding cassette (ABC) proteins, highly conserved transmembrane transporters. An emerging ABC transporters as potential prognostic tools progression invasiveness emphasized. Targeting both proteins holds promise novel therapeutic strategy treatment.

Language: Английский

Citations

1
Reprogramming of tumor-associated macrophages by metabolites generated from tumor microenvironment DOI Creative Commons
Seung Woo Kim, Chan Woo Kim, Young-Ah Moon

et al.

Animal Cells and Systems, Journal Year: 2024, Volume and Issue: 28(1), P. 123 - 136

Published: April 3, 2024

The tumor microenvironment comprises both and non-tumor stromal cells, including tumor-associated macrophages (TAMs), endothelial carcinoma-associated fibroblasts. TAMs, major components of play a crucial role in creating an immunosuppressive environment by releasing cytokines, chemokines, growth factors, immune checkpoint proteins that inhibit T cell activity. During tumors develop, cancer cells release various mediators, chemokines metabolites, recruit monocytes to infiltrate tissues subsequently induce M2-like phenotype tumor-promoting properties. Metabolites are often overlooked as metabolic waste or detoxification products but may contribute TAM polarization. Furthermore, display high degree plasticity among the microenvironment, enabling them either facilitate progression. Therefore, TAM-targeting has emerged promising strategy immunotherapy. This review provides overview multiple representative metabolites involved phenotypes, focusing on their pro-tumoral polarization M2.

Language: Английский

Citations

8
A novel insight into cancer therapy: Lipid metabolism in tumor-associated macrophages DOI Creative Commons

Yvxiao Ren,

Mingjie Wang,

Hanghang Yuan

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 135, P. 112319 - 112319

Published: May 26, 2024

The tumor immune microenvironment (TIME) can limit the effectiveness and often leads to significant side effects of conventional cancer therapies. Consequently, there is a growing interest in identifying novel targets enhance efficacy targeted therapy. More research indicates that tumor-associated macrophages (TAMs), originating from peripheral blood monocytes generated bone marrow myeloid progenitor cells, play crucial role (TME) are closely associated with resistance traditional Lipid metabolism alterations have been widely recognized as having impact on tumors their microenvironment. Lipids, lipid derivatives, key substances metabolic pathways influence carcinogenesis progression cells by modulating phenotype, function, activity TAMs. Therefore, this review focuses reprogramming microenvironment, which TAMs especially concentrated. Such changes activation polarization, thereby affecting cell response treatment. Furthermore, article explores potential targeting supplementary approach It reviews evaluates current strategies for enhancing through TAMs' proposes new synergistic options chemo-radiotherapy immunotherapy. These efforts aim stimulate further area.

Language: Английский

Citations

8