Principles and therapeutics of cancer

Molecules and Cells, Год журнала: 2025, Номер unknown, С. 100201 - 100201

Опубликована: Фев. 1, 2025

Язык: Английский

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Recent advances in chemodynamic nanotherapeutics to overcome multidrug resistance in cancers

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 184, С. 117901 - 117901

Опубликована: Фев. 11, 2025

Язык: Английский

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Single-Cell RNA Sequencing in Unraveling Acquired Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: New Perspectives

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1483 - 1483

Опубликована: Фев. 11, 2025

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated remarkable efficacy in treating non-small cell lung cancer (NSCLC), but acquired resistance greatly reduces and poses a significant challenge to patients. While numerous studies investigated the mechanisms underlying EGFR-TKI resistance, its complexity diversity make existing understanding still incomplete. Traditional approaches frequently struggle adequately reveal process of drug development through mean value analysis at overall cellular level. In recent years, rapid single-cell RNA sequencing technology has introduced transformative method for analyzing gene expression changes within tumor cells resolution. It not only deepens our microenvironment heterogeneity associated with also identifies potential biomarkers resistance. this review, we highlight critical role research, particular focus on application exploring EGFR-TKI-acquired NSCLC. We emphasize elucidating mechanism promise informing more precise personalized treatment strategies. Ultimately, approach aims advance NSCLC toward new era precision medicine.

Язык: Английский

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Application of an Integrated Single-Cell and Three-Dimensional Spheroid Culture Platform for Investigating Drug Resistance Heterogeneity and Epithelial–Mesenchymal Transition (EMT) in Lung Cancer Subclones

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1766 - 1766

Опубликована: Фев. 19, 2025

Lung cancer is a leading cause of cancer-related mortality worldwide, largely due to its heterogeneity and intrinsic drug resistance. Malignant pleural effusions (MPEs) provide diverse tumor cell populations ideal for studying these complexities. Although chemotherapy targeted therapies can be initially effective, subpopulations cells with phenotypic plasticity often survive treatment, eventually developing Here, we integrated single-cell isolation three-dimensional (3D) spheroid culture dissect subclonal responses, aiming inform precision medicine approaches. Using A549 lung cells, established cisplatin-resistant line isolated three resistant subclones (Holoclone, Meroclone, Paraclone) via sorting. In 3D spheroids, Docetaxel Alimta displayed higher IC50 values than in 2D cultures, suggesting that models better reflect clinical dosing. Additionally, MPE-derived Holoclone Paraclone exhibited distinct sensitivities Giotrif Capmatinib, revealing their heterogeneous responses. Molecular analyses confirmed elevated ABCB1, ABCG2, stem (CSC) markers (OCT4, SOX2, CD44, CD133), epithelial-mesenchymal transition (EMT) (E-cadherin downregulation, increased Vimentin, N-cadherin, Twist) subclones, correlating enhanced migration invasion. This approach clarifies the interplay between heterogeneity, CSC/EMT phenotypes, resistance, providing valuable tool predicting therapeutic responses guiding personalized, combination-based treatments.

Язык: Английский

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Tumor cells that resist neutrophil anticancer cytotoxicity acquire a prometastatic and innate immune escape phenotype

Cellular and Molecular Immunology, Год журнала: 2025, Номер unknown

Опубликована: Март 28, 2025

In the tumor host, neutrophils may exhibit protumor or antitumor activity. It is hypothesized that in response to host-derived therapy-induced factors, adopt diverse functional states ultimately execute these differential functions. Here, we provide an alternative scenario which of individual cell population determines overall versus outcome neutrophil‒tumor interactions. Experimentally, show human neutrophils, are sequentially stimulated with bacteria and secreted factors from cells, kill a certain proportion target cells. However, majority cells remained resistant this neutrophil-mediated killing underwent functional, phenotypic transcriptomic switch was reminiscent partial epithelial‒to-mesenchymal transition. This biological associated physical escape NK-mediated resulted enhanced metastasis lymph nodes preclinical orthotopic mouse model. Mechanistically, identified antimicrobial neutrophil granule proteins elastase (NE) matrix metalloprotease-9 (MMP-9) as molecular mediators switch. We validated data patients head neck cancer bacterially colonized intratumoral niches were enriched for mesenchymal expressing NE MMP-9. Our reveal parallel execution cytotoxic prometastatic activity by activated identify MMP-9 node metastasis. The mechanism explains dichotomy tumor-associated at level has implications superinfected cancers dysbiotic microenvironment.

Язык: Английский

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Characteristic, Regulation and Targeting Strategies of Cancer Stem Cells and Their Niche in Digestive System Tumors

MedComm – Oncology, Год журнала: 2025, Номер 4(2)

Опубликована: Апрель 8, 2025

ABSTRACT Digestive system tumor, including esophageal gastric intestinal liver pancreatic and cholangiocarcinoma, are the most common tumors worldwide serve as a major cause of tumor‐related death. Cancer stem cells (CSCs) small group in that harbor self‐renewal, differentiation abilities, playing crucial role tumor initiation, progression, metastasis, supposed to be fundamental recurrence after conventional treatment. A comprehensive understanding targeting CSCs is key overcoming tumors. In this review, focusing on digestive tumors, we summarize characteristics CSCs, review intracellular mechanisms regulate self‐renewal functional maintenance stemness pathways, transcription epigenetic regulation, metabolic noncoding RNAs, demonstrate microenvironmental regulation systemic at molecular cellular levels. Finally, recent advances therapy with CSC their niche remodeling. These research progress provide insights into occurrence, development, drug resistance, metastasis offers new targeted treatment strategies for defeating

Язык: Английский

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Proteomic-based stemness score measures oncogenic dedifferentiation and enables the identification of druggable targets

Cell Genomics, Год журнала: 2025, Номер unknown, С. 100851 - 100851

Опубликована: Апрель 1, 2025

Cancer progression and therapeutic resistance are closely linked to a stemness phenotype. Here, we introduce protein-expression-based index (PROTsi) evaluate oncogenic dedifferentiation in relation histopathology, molecular features, clinical outcomes. Utilizing datasets from the Clinical Proteomic Tumor Analysis Consortium across 11 tumor types, validate PROTsi's effectiveness accurately quantifying stem-like features. Through integration of PROTsi with multi-omics, including protein post-translational modifications, identify features associated proteins that act as active nodes within transcriptional networks, driving aggressiveness. Proteins highly correlated were identified potential drug targets, both shared specific. These stemness-associated demonstrate predictive value for outcomes, confirmed by immunohistochemistry multiple samples. The findings emphasize efficacy valuable tool selecting crucial step customizing anti-cancer therapy advancing development cures cancer patients.

Язык: Английский

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KSR1 regulates small-cell lung carcinoma tumor initiation and cisplatin resistance

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 26, 2024

Abstract Small-cell lung cancer (SCLC) has a dismal five-year survival rate of less than 7%, with limited advances in first line treatment over the past four decades. Tumor-initiating cells (TICs) contribute to resistance and relapse, major impediment SCLC treatment. Here, we identify Kinase Suppressor Ras 1 (KSR1), molecular scaffold for Raf/MEK/ERK signaling cascade, as critical regulator TIC formation tumor initiation vivo . We further show that KSR1 mediates cisplatin SCLC. While 50-70% control after 6-week exposure cisplatin, CRISPR/Cas9-mediated knockout prevents >90% ASCL1, NeuroD1, POU2F3 subtypes. KO significantly enhances ability decrease TICs via vitro extreme limiting dilution analysis (ELDA), indicating disruption toxicity responsible therapeutic initiation. The prevent resistant H82 xenograft supports this conclusion. Previous studies indicate ERK activation inhibits growth development. observe minimal effect pharmacological inhibition on no impact ELDA. However, mutational DEF domain, which interaction ERK, suggests is essential KSR1-driven resistance. These findings reveal key regulatory protein biology potential target across multiple Statement Implication Genetic manipulation small-cell reveals its contribution

Язык: Английский

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CMINNs: Compartment model informed neural networks — Unlocking drug dynamics

Computers in Biology and Medicine, Год журнала: 2024, Номер 184, С. 109392 - 109392

Опубликована: Ноя. 28, 2024

Язык: Английский

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Modulation of the Cytoskeleton for Cancer Therapy

Опубликована: Янв. 1, 2024

Язык: Английский

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