Signaling, cancer cell plasticity, and intratumor heterogeneity

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

Published: May 3, 2024

Abstract Cancer’s complexity is in part due to the presence of intratumor heterogeneity and dynamic nature cancer cell plasticity, which create substantial obstacles effective management. Variability within a tumor arises from existence diverse populations cells, impacting progression, spread, resistance treatments. At core this variability concept cellular plasticity - intrinsic ability cells alter their molecular identity reaction environmental genetic changes. This adaptability cornerstone cancer’s persistence making it formidable target for Emerging studies have emphasized critical role such fostering diversity, turn influences course disease effectiveness therapeutic strategies. The transformative involves network signal transduction pathways, notably those that drive epithelial-to-mesenchymal transition metabolic remodeling, shaping evolutionary path cells. Despite advancements, our understanding precise machinations signaling networks driving these changes still evolving, underscoring necessity further research. editorial presents series entitled “Signaling Cancer Cell Plasticity Intratumor Heterogeneity” Communication Signaling, dedicated unraveling complex processes proposing new avenues intervention.

Language: Английский

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Emerging Role of Extracellular pH in Tumor Microenvironment as a Therapeutic Target for Cancer Immunotherapy

Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1924 - 1924

Published: Nov. 20, 2024

Identifying definitive biomarkers that predict clinical response and resistance to immunotherapy remains a critical challenge. One emerging factor is extracellular acidosis in the tumor microenvironment (TME), which significantly impairs immune cell function contributes failure. However, acidic conditions TME disrupt interaction between cancer cells, driving tumor-infiltrating T cells NK into an inactivated, anergic state. Simultaneously, promotes recruitment activation of immunosuppressive such as myeloid-derived suppressor regulatory (Tregs). Notably, acidity enhances exosome release from Tregs, further amplifying immunosuppression. Tumor thus acts "protective shield," neutralizing anti-tumor responses transforming pro-tumor allies. Therefore, targeting lactate metabolism has emerged promising strategy overcome this barrier, with approaches including buffer agents neutralize pH inhibitors block production or transport, thereby restoring efficacy TME. Recent discoveries have identified genes involved (pHe) regulation, presenting new therapeutic targets. Moreover, ongoing research aims elucidate molecular mechanisms acidification develop treatments modulate levels enhance outcomes. Additionally, future studies are crucial validate safety pHe-targeted therapies patients. Thus, review explores regulation pHe its potential role improving immunotherapy.

Language: Английский

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Smartphone-assisted immunosensing of cancer biomarkers in human biofluids using poly (methyl methacrylate) decorated by triangular silver nanoparticles

Journal of Photochemistry and Photobiology A Chemistry, Journal Year: 2024, Volume and Issue: 457, P. 115882 - 115882

Published: July 10, 2024

Language: Английский

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Enhancing Radiation Therapy Response in Prostate Cancer Through Metabolic Modulation by Mito-Lonidamine: A 1H and 31P Magnetic Resonance Spectroscopy Study

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 509 - 509

Published: Jan. 9, 2025

Radiation therapy (RT) is the cornerstone treatment for prostate cancer; however, it frequently induces gastrointestinal and genitourinary toxicities that substantially diminish patients' quality of life. While many individuals experience transient side effects, a subset endures persistent, long-term complications. A promising strategy to mitigate these involves enhancing tumor radiosensitivity, potentially allowing lower radiation doses. In this context, mito-lonidamine (Mito-LND), an antineoplastic agent targeting mitochondrial electron transport chain's complexes I II, emerges as potential radiosensitizer. This study investigated Mito-LND's capacity augment RT efficacy reduce adverse effects through comprehensive in vitro vivo assessments using hormone-sensitive hormone-refractory cancer models. Employing Seahorse analysis 1H/31P magnetic resonance spectroscopy (MRS), we observed Mito-LND selectively suppressed lactate production, decreased intracellular pH, reduced bioenergetics oxygen consumption levels within cells. These findings suggest remodels microenvironment by inducing acidification, metabolic de-energization, enhanced oxygenation, thereby sensitizing tumors RT. Our results underscore therapeutic adjunct improve patient outcomes radiation-associated early-stage cancer.

Language: Английский

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Pan‑cancer analysis of the oncogenic role of telomeric repeat binding factor 2 (TERF2) in human tumors and in vitro validation in gastric cancer by TERF2 knockdown

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

Published: Feb. 24, 2025

Telomeric repeat binding factor 2 (TERF2), a key component of the Shelterin complex, is crucial for maintaining telomere integrity and genome stability. While involvement TERF2 in tumorigenesis progression has been documented, comprehensive pan-cancer analyses across different malignancies remain scarce. In present study, expression, mutations, immune cell infiltration, interacting genes were systematically evaluated through bioinformatics analysis, vitro experiments performed to elucidate functional roles gastric cancer. The findings revealed that was predominantly upregulated cholangiocarcinoma (CHOL), diffuse large B-cell lymphoma (DLBC), pancreatic adenocarcinoma (PAAD), stomach (STAD), thymoma (THYM), correlating with tumor progression. Amplification mutations identified as primary alterations TERF2, particularly associated liver hepatocellular carcinoma (LIHC). Furthermore, expression linked infiltration cancer-associated fibroblasts cells certain cancer types. Protein–protein interaction (PPI) analysis highlighted several including CTCF, DDX19A, MATR3, ZFP1, ZFP90. Additionally, demonstrated knockdown significantly suppressed proliferation migration cells. These results suggest dysregulation are prevalent various cancers, contributing immunity acting an oncogenic factor, thus positioning potential therapeutic target treatment.

Language: Английский

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Mitigating ambient RNA and doublets effects on single cell transcriptomics analysis in cancer research

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217693 - 217693

Published: April 1, 2025

Language: Английский

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Transcriptomic signatures of prostate cancer progression: a comprehensive RNA-seq study

3 Biotech, Journal Year: 2025, Volume and Issue: 15(5)

Published: April 19, 2025

Language: Английский

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Modeling of cancer stem cells and the tumor microenvironment Via NT2/D1 cells to probe pathology and treatment for cancer and beyond

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

Published: April 24, 2025

Language: Английский

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Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions

Biomolecules, Journal Year: 2024, Volume and Issue: 14(6), P. 649 - 649

Published: May 31, 2024

The p53 protein is the master regulator of cellular integrity, primarily due to its tumor-suppressing functions. Approximately half all human cancers carry mutations in TP53 gene, which not only abrogate tumor-suppressive functions but also confer mutant proteins with oncogenic potential. latter achieved through so-called gain-of-function (GOF) that promote cancer progression, metastasis, and therapy resistance by deregulating transcriptional networks, signaling pathways, metabolism, immune surveillance, compositions microenvironment. Despite recent progress understanding complexity mutp53 neoplastic development, exact mechanisms how contributes development they escape proteasomal lysosomal degradation remain partially understood. In this review, we address findings field specifically regarding, limited to, implications metabolic secretome cells, microenvironment, regulating scenarios aberrant degradation. By analyzing degradation, as well connection autophagy, propose new therapeutical approaches aim destabilize deactivate functions, thereby providing a fundamental basis for further investigation rational treatment TP53-mutated cancers.

Language: Английский

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Stemness regulation in prostate cancer: prostate cancer stem cells and targeted therapy

Annals of Medicine, Journal Year: 2024, Volume and Issue: 57(1)

Published: Dec. 23, 2024

Background Increasing evidence indicates that cancer stem cells (CSCs) and stem-like form a special subpopulation of are ubiquitous in tumors. These exhibit similar characteristics to those normal tissues; moreover, they capable self-renewal differentiation, as well high tumorigenicity drug resistance. In prostate (PCa), it is difficult kill these using androgen signaling inhibitors chemotherapy drugs. Consequently, the residual (PCSCs) mediate tumor recurrence progression.

Language: Английский

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