Cancer metabolism and carcinogenesis

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 29, 2024

Abstract Metabolic reprogramming is an emerging hallmark of cancer cells, enabling them to meet increased nutrient and energy demands while withstanding the challenging microenvironment. Cancer cells can switch their metabolic pathways, allowing adapt different microenvironments therapeutic interventions. This refers heterogeneity, in which cell populations use pathways sustain survival proliferation impact response conventional therapies. Thus, targeting heterogeneity represents innovative avenue with potential overcome treatment resistance improve outcomes. review discusses patterns developmental stages, summarizes molecular mechanisms involved intricate interactions within metabolism, highlights clinical vulnerabilities as a promising regimen. We aim unravel complex characteristics develop personalized approaches address distinct traits, ultimately enhancing patient

Language: Английский

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Hallmarks of cancer resistance

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109979 - 109979

Published: May 15, 2024

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized Warburg effect, and dynamic interplay between cells mitochondria. The role stem (CSCs) in treatment resistance regulatory influence non-coding RNAs, such as long RNAs (lncRNAs), microRNAs (miRNAs), circular (circRNAs), are studied. chapter emphasizes future directions, encompassing advancements immunotherapy, strategies to counter adaptive integration artificial intelligence for predictive modeling, identification biomarkers personalized treatment. comprehensive exploration these provides a foundation innovative therapeutic approaches, aiming navigate complex landscape enhance patient outcomes.

Language: Английский

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Allogeneic CD33-directed CAR-NKT cells for the treatment of bone marrow-resident myeloid malignancies

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 1, 2025

Abstract Chimeric antigen receptor (CAR)-engineered T cell therapy holds promise for treating myeloid malignancies, but challenges remain in bone marrow (BM) infiltration and targeting BM-resident malignant cells. Current autologous CAR-T therapies also face manufacturing patient selection issues, underscoring the need off-the-shelf products. In this study, we characterize primary samples identify a unique therapeutic opportunity CAR-engineered invariant natural killer (CAR-NKT) Using stem gene engineering clinically guided culture method, generate allogeneic CD33-directed CAR-NKT cells with high yield, purity, robustness. preclinical mouse models, exhibit strong BM homing effectively target blast cells, including CD33-low/negative leukemia progenitor Furthermore, synergize hypomethylating agents, enhancing tumor-killing efficacy. These show minimal off-tumor toxicity, reduced graft-versus-host disease cytokine release syndrome risks, resistance to allorejection, highlighting their substantial potential malignancies.

Language: Английский

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Boosting CAR-T cell therapy through vaccine synergy

Trends in Pharmacological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape for hematological cancers. However, achieving comparable success in solid tumors remains challenging. Factors contributing to these limitations include scarcity of tumor-specific antigens (TSAs), insufficient CAR-T infiltration, and immunosuppressive tumor microenvironment (TME). Vaccine-based strategies are emerging as potential approaches address challenges, enhancing expansion, persistence, antitumor efficacy. In this review, we explore diverse vaccine modalities, including mRNA, peptide, viral vector, dendritic (DC)-based vaccines, their roles augmenting responses. Special focus is given recent clinical advancements combining mRNA-based vaccines with genitourinary addition, discuss crucial considerations optimizing dosing, scheduling, delivery maximize synergy, aiming refine combination strategy improve efficacy safety.

Language: Английский

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Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence

Military Medical Research, Journal Year: 2025, Volume and Issue: 12(1)

Published: Feb. 11, 2025

Abstract Cancer recurrence, driven by the phenomenon of tumor dormancy, presents a formidable challenge in oncology. Dormant cancer cells have ability to evade detection and treatment, leading relapse. This review emphasizes urgent need comprehend dormancy its implications for recurrence. Despite notable advancements, significant gaps remain our understanding mechanisms underlying lack reliable biomarkers predicting provides comprehensive analysis cellular, angiogenic, immunological aspects dormancy. It highlights current therapeutic strategies targeting dormant cells, particularly combination therapies immunotherapies, which hold promise preventing By elucidating these proposing innovative research methodologies, this aims deepen ultimately facilitating development more effective recurrence improving patient outcomes.

Language: Английский

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Frontiers in pancreatic cancer on biomarkers, microenvironment, and immunotherapy

Cancer Letters, Journal Year: 2024, Volume and Issue: unknown, P. 217350 - 217350

Published: Nov. 1, 2024

Pancreatic cancer remains one of the most challenging malignancies to treat due its late-stage diagnosis, aggressive progression, and high resistance existing therapies. This review examines latest advancements in early detection, therapeutic strategies, with a focus on emerging biomarkers, tumor microenvironment (TME) modulation, integration artificial intelligence (AI) data analysis. We highlight promising including microRNAs (miRNAs) circulating DNA (ctDNA), that offer enhanced sensitivity specificity for early-stage diagnosis when combined multi-omics panels. A detailed analysis TME reveals how components such as cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix (ECM) contribute therapy by creating immunosuppressive barriers. also discuss interventions target these components, aiming improve drug delivery overcome evasion. Furthermore, AI-driven analyses are explored their potential interpret complex data, enabling personalized treatment strategies real-time monitoring response. conclude identifying key areas future research, clinical validation regulatory frameworks AI applications, equitable access innovative comprehensive approach underscores need integrated, outcomes pancreatic cancer.

Language: Английский

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Deciphering the Role of Cancer Stem Cells: Drivers of Tumor Evolution, Therapeutic Resistance, and Precision Medicine Strategies

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 382 - 382

Published: Jan. 24, 2025

Cancer stem cells (CSCs) play a central role in tumor progression, recurrence, and resistance to conventional therapies, making them critical focus oncology research. This review provides comprehensive analysis of CSC biology, emphasizing their self-renewal, differentiation, dynamic interactions with the microenvironment (TME). Key signaling pathways, including Wnt, Notch, Hedgehog, are discussed detail highlight potential as therapeutic targets. Current methodologies for isolating CSCs critically examined, addressing advantages limitations advancing precision medicine. Emerging technologies, such CRISPR/Cas9 single-cell sequencing, explored transformative unraveling heterogeneity informing strategies. The also underscores pivotal TME supporting survival, promoting metastasis, contributing resistance. Challenges arising from CSC-driven dormancy analyzed, along strategies mitigate these barriers, novel therapeutics targeted approaches. Ethical considerations integration artificial intelligence designing CSC-specific therapies essential elements future manuscript advocates multi-disciplinary approach that combines innovative advanced therapeutics, collaborative research address complexities CSCs. By bridging existing gaps knowledge fostering advancements personalized medicine, this aims guide development more effective cancer treatment strategies, ultimately improving patient outcomes.

Language: Английский

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Cancer stem cell populations are resistant to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT)

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 5, 2025

Photodynamic therapy (PDT) is a minimally invasive treatment approved for many types of cancers. PDT involves the administration photoactive substances called photosensitizers (PS) that selectively accumulate in cancer cells and are subsequently excited/activated by irradiation with light at wavelengths optimal absorbance. Activated PS leads to generation singlet oxygen other reactive species (ROS), promoting cell death. 5-aminolevulinic acid (5-ALA) naturally occurring precursor, which metabolically converted PS, protoporphyrin IX (PPIX). Although 5-ALA-PDT effective killing cells, prior studies conducted our group we normally observed vitro experiments approximately 5–10% survive 5-ALA-PDT, served as an impetus further investigation. Identifying mechanisms resistance 5-ALA-PDT-mediated death important prevent tumor recurrence following 5-ALA-PDT. Previously, reported oncogenic activation Ras/MEK promotes PPIX efflux reduces cellular sensitivity through increased expression ABCB1 transporter. As stem (CSCs) known drive treatments have high chemotherapeutic agents via ABC-family transporters, hypothesize CSCs underlie resistance. In this study, determined (1) if resistant (2) play roles establishing populations When compared CSC before after found were less susceptible Moreover, population was enriched 5-ALA-PDT-resistant lines parental line. Our results indicate not sensitive may contribute establishment

Language: Английский

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Adiponectin Influences the Behavior of Stem Cells in Hormone-Resistant Breast Cancer

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 286 - 286

Published: Feb. 15, 2025

In the breast tumor microenvironment (TME), adipocytes exert a selective pressure on behavior of cancer stem cells (BCSCs), which are involved in endocrine therapy resistance. obesity, secrete reduced levels adiponectin, promotes growth and progression ERα-positive (BC). Here, we examined how low adiponectin affect enrichment BCSC subpopulation mechanisms contributing to maintenance resistance BC. Flow cytometry, qRT-PCR, Western blotting analysis were performed assess stemness, cell cycle, apoptosis markers MCF-7 wild-type (WT) tamoxifen-resistant (TR) mammospheres. nLC-MS/MS was employed profile compare proteome BCSCs. Differentially expressed proteins intersected with data from MetacoreTM dataset. Our study demonstrated that increased percentage CD44+/CD24-/ALDH1+ stem-like TR Specifically, contributed bulk through slow cycling rate, supported by decreased Cyclin D1 Ki67 p21 p27 expression, escape apoptosis, sustained ROS production preserved mitochondrial membrane potential. results provide new insights into contribution poor BC outcomes. Deeply understanding adiponectin's role stemness may disclose novel therapeutic approaches treat hormone-resistant obese patients.

Language: Английский

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Unveiling the future of cancer stem cell therapy: a narrative exploration of emerging innovations

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 22, 2025

Cancer stem cells (CSCs), are a critical subpopulation within tumours, and defined by their capacity for self-renewal, differentiation, tumour initiation. These unique traits contribute to progression, metastasis, resistance conventional treatments like chemotherapy radiotherapy, often resulting in cancer recurrence poor patient outcomes. As such, CSCs have become focal points developing advanced therapies. This review highlights progress CSC-targeted treatments, including chimeric antigen receptor T-cell (CAR-T) therapy, immunotherapy, molecular targeting, nanoparticle-based drug delivery systems. Plant-derived compounds gene-editing technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR), explored potential enhance precision minimize side effects. Metabolic pathways integral CSC survival, mitochondrial dynamics, mitophagy (regulated dynamin-related protein 1 [DRP1] the PINK1/Parkin pathway), one-carbon metabolism, amino acid metabolism (involving enzymes glutaminase (GLS) glutamate dehydrogenase (GDH]), lipid hypoxia-induced metabolic reprogramming mediated hypoxia-inducible factors (HIF-1α HIF-2α), examined therapeutic targets. The adaptability of through autophagy, flexibility, epigenetic regulation metabolites α-ketoglutarate, succinate, fumarate is discussed. Additionally, extracellular vesicles nicotinamide adenine dinucleotide (NAD⁺) identified pivotal redox balance, DNA repair, modifications. Addressing challenges heterogeneity, immune evasion, treatment durability requires interdisciplinary collaboration. Advancing therapies essential overcoming preventing relapse, paving way transformative treatments. underscores importance leveraging innovative technologies fostering collaboration revolutionize treatment.

Language: Английский

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