Pancreatic and Hepatic Oncology Research

Loss of p21-activated kinase 4 (PAK4) suppresses pancreatic tumor progression and metastasis through regulating E-cadherin

This study shows that PAK4 promotes pancreatic cancer metastasis by reducing E-cadherin, and its loss inhibits tumor progression and metastasis.

Long-range chromatin interactions nominate candidate susceptibility genes at non-coding PDAC risk loci

The paper fine-maps GWAS risk variants for PDAC and identifies candidate target genes through chromatin conformation capture, finding functional interactions and eQTLs at specific loci.

Keratin 17 Defines an Epithelial-Mesenchymal Transition-Associated Migratory Cell State in Pancreatic Ductal Adenocarcinoma

This study identifies K17 as a marker of an EMT-associated migratory cell state in PDAC, showing its role in promoting tumor-cell migration and poor prognosis.

Multiplex-GCN Predicts Clinically Actionable Tumor Microenvironment Subtypes in Pancreatic Cancer

The paper develops a multi-layered GCN to identify TME-guided PDAC subtypes, revealing seven subtypes with distinct molecular and prognostic features.

Tumour-stroma signaling drives a reversible program with neural-like features in cancer-associated fibroblasts

The paper identifies tumor-derived signals that induce a reversible neural-like program in cancer-associated fibroblasts and shows it is regulated by growth factors and MAPK/ERK signaling.

The impact of sex and ancestry on the molecular landscape of pancreatic adenocarcinoma

This study examines how sex and ancestry influence the genomic heterogeneity of pancreatic adenocarcinoma across multiple datasets.

Loss of the Y chromosome drives basal identity and metastatic potential via epigenetic reprogramming in pancreatic cancer

This study identifies LOY as a driver of aggressive PDAC through epigenetic reprogramming, linking it to EMT and metastasis, and highlights its clinical relevance as a biomarker.

Distinct Progression Paths Underlie the Diversity of Pancreatic Papillary Cystic Neoplasms

The paper identifies distinct progression paths in pancreatic papillary cystic neoplasms using integrated transcriptomics and histology, enabling phenotype-specific prediction of high-grade dysplasia.

Pulsed Field Ablation Enables Stromal Manipulation and Tumor Reduction in Pancreatic Ductal Adenocarcinoma

This study shows pulsed field ablation (PFA) reduces tumor growth in a mouse model of pancreatic ductal adenocarcinoma by altering the tumor microenvironment and stromal cells.

HMGA2 Expression in Pancreatic Ductal Adenocarcinoma Controls Tumor Microenvironment and Immunosuppression via IL1α

This study shows HMGA2 in PDAC drives immunosuppressive TME by upregulating IL1α, which promotes CAFs and reduces CD8+ T cells, and blocking IL1 improves tumor control with KRAS inhibitors.

KRAS inhibition drives adaptive surfaceome remodeling and reveals ALPP/ALPPL2 as a targetable vulnerability in pancreatic cancer

This study identifies ALPP/ALPPL2 as a targetable vulnerability in pancreatic cancer by analyzing proteomic changes induced by KRAS inhibition and developing an antibody drug conjugate.

Epigenetic progression of pancreatic cancer to aggressive subtypes involves alternate routes of lineage reprogramming in subtype-intermediate progenitor cells

The paper identifies subtype-intermediate progenitor cells in pancreatic cancer with distinct epigenetic profiles linked to clinical outcomes and lineage reprogramming.

Context-specific genetic interaction mapping reveals combinatorial KRAS/FGFR dependence in pancreatic cancer

The paper identifies combinatorial KRAS/FGFR dependence in pancreatic cancer through genetic interaction mapping and shows that combined inhibition overcomes resistance.

Longitudinal Analysis of Matched Patient Biospecimens Reveals Neural Reprogramming of Cancer-Associated Fibroblasts Following Chemotherapy in Pancreatic Cancer

The paper analyzes matched pre- and post-chemotherapy biospecimens in pancreatic cancer, revealing that cancer-associated fibroblasts undergo neural reprogramming, characterized by axonal guidance gene enrichment, which may contribute to chemoresistance and tumor progression.

Conserved Metastatic Cell States and Spatial Immune Microenvironment Remodeling Define Pancreatic Cancer Liver Metastases

The paper identifies conserved transcriptional programs in pancreatic cancer liver metastases and shows how they interact with spatial immune microenvironments to drive metastatic progression.

MetScore and classical-basal subtype intersect to define chemotherapy response and tumor microenvironment architecture in pancreatic ductal adenocarcinoma

The paper integrates MetScore with classical-basal subtype to better explain PDAC metastasis, prognosis, treatment response, and tumor microenvironment than a single-axis model.

Neoadjuvant chemotherapy induces transient, regimen-specific immune stromal reprogramming in pancreatic ductal adenocarcinoma

This study shows that neoadjuvant chemotherapy temporarily changes the immune and stromal environment in pancreatic cancer based on the treatment regimen and timing.

A Full Spectrum Fibroblast Profiling Panel Reveals Phenotypic and Metabolic Heterogeneity of Cancer-Associated Fibroblasts at the Single-Cell Level

This paper introduces a 28-marker flow cytometry panel to profile cancer-associated fibroblasts (CAFs) and reveals their phenotypic and metabolic heterogeneity across different models.

TGF-β- and IL-1-dependent fibroblast states differentially shape pancreatic cancer microenvironments and metastasis

This study shows that TGF-β-dependent myCAFs promote pancreatic cancer metastasis, while IL-1-dependent iCAFs do not, through distinct signaling mechanisms.

PPARδ Expression and Prognosis in Resected Pancreatic Cancer: A Retrospective Single-Centre Study

This study examines PPARδ expression in resected pancreatic cancer specimens and finds an association with adverse clinicopathological features and poorer survival.

Transcriptomic FOLFIRINOX sensitivity signatures stratify overall survival and reveal directional reclassification after neoadjuvant FOLFIRINOX in borderline resectable and locally advanced pancreatic cancer

This paper evaluates transcriptomic FOLFIRINOX sensitivity signatures in neoadjuvant pancreatic cancer, finding they predict survival and show directional reclassification after treatment.

Spatial multi-omics resolve epithelium-fibroblast gradients and highlight NESTIN-NOTCH1-expressing subepithelial fibroblasts during human pancreatic tumorigenesis

This study uses spatial multi-omics to identify NESTIN-NOTCH1-expressing fibroblasts in IPMNs and their role in pancreatic tumorigenesis.

Comparative Analysis of Primary and Liver Fibroblasts Reveals MET as a Potent Target in Pancreatic Cancer Metastasis

The paper compares primary and liver PDAC lesions using single-cell transcriptomics to identify MET as a target in pancreatic cancer metastasis.

Extravascular coagulation stabilizes pro-fibrotic stromal states via tumor-intrinsic PAR1 signaling in pancreatic ductal adenocarcinoma

This study identifies extravascular coagulation as a regulator of fibrotic stromal states in PDAC via tumor-intrinsic PAR1 signaling, showing PAR1 inhibition can reprogram the tumor-promoting stroma.

Multi-stromal organoid co-cultures model pancreatic cancer and pancreatitis epithelial cell-fibroblast heterogeneity

This study compares fibroblast heterogeneity in pancreatic cancer and pancreatitis using organoid co-cultures and identifies distinct stromal reprogramming in each condition.

Benchmarking the Intratumoral Microbiome in Pancreatic Ductal Adenocarcinoma: A Longitudinal Assessment of Contamination Sources and Decontamination Strategies

This study benchmarks decontamination methods for intratumoral microbiome analysis in PDAC, finding the Nj pipeline outperforms others in reducing contamination while preserving tumor signals.

Continuous tissue fields organize immune composition in pancreatic cancer

This study identifies continuous spatial organization of immune composition and tumor identity in pancreatic cancer using spatial transcriptomics and single-cell imaging.

Inositol Polyphosphate-4-Phosphatase Type II promotes gemcitabine resistance in pancreatic ductal adenocarcinoma cells via lysosomal exocytosis

This study shows INPP4B promotes gemcitabine resistance in PDAC by enhancing lysosomal exocytosis, which can be reversed by lysosome-targeting drugs.

L1CAMxCD3 bispecific antibodies exert potent anti-tumor effects in preclinical pancreatic cancer models considering the complex tumor stroma

This study shows L1CAMxCD3 bispecific antibodies effectively target PDAC cells in immunosuppressive models, inducing apoptosis and T cell effector molecule release.

SPINK1-COL18A1 Crosstalk Shapes Epigenome and Drives Cancer Stemness in Pancreatic Ductal Adenocarcinoma

This study identifies SPINK1 as a regulator of epigenomic states and stemness in PDAC through its interaction with COL18A1 and endostatin release.