Modeling the Transitional Phase of Epithelial Cells Reveals Prognostic and Therapeutic Targets in Pancreatic Ductal Adenocarcinoma DOI Open Access
Linhan Ye, Zongyao Chen, Jingcheng Zhang

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(11), P. 1813 - 1813

Published: May 29, 2025

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis, and its progression driven by epithelial plasticity tumor microenvironment remodeling. Finding biomarkers that are responsible for the turning point from early stage to phase would facilitate clinical management. Method: In this study, we employed single-cell RNA sequencing characterize distinct subpopulation of proliferative cells undergoing transitional during PDAC progression. By linking cell cycle dysregulation, differentiation, staging, constructed gene-based risk score model using Lasso Cox regression. The expression selected genes within was further validated qPCR. Results: demonstrated robust predictive power patient TNM chemotherapy sensitivity. Further analysis revealed intensified crosstalk between specific fibroblast cells, mediated largely collagen signaling. This stromal-epithelial interaction found contribute fibrotic barrier characteristic PDAC. Additionally, immune profiling uncovered altered infiltration patterns, particularly involving natural killer (NK) in high-risk patients, suggesting mechanisms tolerance inhibition. Conclusions: These findings offer potential avenues detection, stratification, targeted therapeutic strategies

Language: Английский

Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge DOI Creative Commons
Ruth Nussinov, Bengi Ruken Yavuz, Hyunbum Jang

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169050 - 169050

Published: Feb. 1, 2025

Language: Английский

Citations

2
Farnesyl Transferase Inhibitors as a Novel Strategy for Targeting KRAS-Dependent Cancers DOI Creative Commons
Robert B. Kargbo

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: 16(4), P. 517 - 519

Published: March 11, 2025

KRAS mutations drive tumorigenesis in multiple cancers, yet direct inhibitors display limited efficacy due to adaptive resistance. Recent preclinical findings indicate farnesyl transferase (FTIs) can reduce compensatory mTOR and MAPK pathway activation. Evidence supports combining FTIs with enhance tumor suppression delayed

Language: Английский

Citations

0
CD44-Targeted nanoparticles for remodeling the tumor microenvironment in a 3D Macrophage-Embedded ovarian cancer model with stem Cell-Like features DOI

Samjhana Shrestha,

Anil K. Giri,

Prabhat Shrestha

et al.

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125483 - 125483

Published: March 1, 2025

Language: Английский

Citations

0
Modeling the Transitional Phase of Epithelial Cells Reveals Prognostic and Therapeutic Targets in Pancreatic Ductal Adenocarcinoma DOI Open Access
Linhan Ye, Zongyao Chen, Jingcheng Zhang

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(11), P. 1813 - 1813

Published: May 29, 2025

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis, and its progression driven by epithelial plasticity tumor microenvironment remodeling. Finding biomarkers that are responsible for the turning point from early stage to phase would facilitate clinical management. Method: In this study, we employed single-cell RNA sequencing characterize distinct subpopulation of proliferative cells undergoing transitional during PDAC progression. By linking cell cycle dysregulation, differentiation, staging, constructed gene-based risk score model using Lasso Cox regression. The expression selected genes within was further validated qPCR. Results: demonstrated robust predictive power patient TNM chemotherapy sensitivity. Further analysis revealed intensified crosstalk between specific fibroblast cells, mediated largely collagen signaling. This stromal-epithelial interaction found contribute fibrotic barrier characteristic PDAC. Additionally, immune profiling uncovered altered infiltration patterns, particularly involving natural killer (NK) in high-risk patients, suggesting mechanisms tolerance inhibition. Conclusions: These findings offer potential avenues detection, stratification, targeted therapeutic strategies

Language: Английский

Citations

0