F. Notta

Abstract A105: The PASS-01 Challenge: Comparing Biomarkers for Treatment Selection in Advanced Pancreatic Cancer in a Randomized Controlled Trial

Predictive biomarkers for first-line treatment selection in advanced pancreatic ductal adenocarcinoma (PDAC) have been proposed, but none have been validated using data from a randomized controlled trial (RCT), which is the only design capable of unbiased assessment of differential treatment effect (DTE)....

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

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

Abstract B026: Multimodal spatial profiling uncovers cell state–associated receptor–ligand interactions in pancreatic ductal adenocarcinoma

Malignant cells do not exist in isolation. In pancreatic ductal adenocarcinoma (PDAC), malignant cells reside within distinct spatial niches shaped by stromal, immune, endothelial, and neural compartments, and this spatial context is linked to therapeutic resistance and clinical outcome. While genomic alterations dri...

Abstract PR007: Integrated spatial proteomics of human PDAC uncovers an expanded tumour-immune-stroma spectrum with genomic associations

Pancreatic ductal adenocarcinoma (PDAC) exhibits extensive cellular and molecular heterogeneity. How unique malignant states interact with and organize local microenvironments to drive therapy resistance and progression remains poorly understood, limiting tumour profiling and patient stratification. Existing binary t...

Abstract A140: Patient-derived organoids and precision medicine: Insights from the PASS-01 clinical trial in PDAC

Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at an advanced stage with limited treatment options. Patient-derived organoids (PDOs) can model tumors, identify determinants of therapeutic response, and support precision medicine. In the multi-institutional PASS-01 trial of metastatic PDAC, biopsies f...

Abstract B066: Convergent cell-state programs characterize BRCA2 -reversion-independent resistance in pancreatic cancer

This work modeled resistance using patient-derived xenografts from two PDACs harboring pathogenic germline BRCA2 variants, and identified convergent transcriptional and epigenetic cell states associated with BRCA2-reversion-independent platinum/PARPi resistance in PDAC.

Abstract A027: Loss of the Y chromosome drives basal identity and metastatic potential via epigenetic reprogramming in pancreatic cancer

It is demonstrated for the first time that LOY is significantly enriched in advanced-stage disease and the aggressive basal molecular subtype, establishing LOY as a causal genetic driver of PDAC progression, acting through epigenetic remodeling to promote EMT, basal subtype identity, metastasis, and therapy resistance.

Abstract B011: HMGA2 controls fibroblast skewing and immune infiltration in basal pancreatic cancer

The role of tumoral HMGA2 expression in controlling an immunosuppressive TME is demonstrated, a potential biomarker to determine TME phenotype in PDAC patients is highlighted and a novel subtype-specific immunomodulatory therapy is introduced.

Multimodal Machine Learning for Predicting Outcomes in the PASS-01 Trial of Systemic Therapy for Metastatic Pancreatic Cancer

MULTIPL demonstrated robust prognostic performance in external validation, identified a subgroup enriched for benefit from GNP, and enabled discovery and validation of prognostic biomarkers in metastatic PDAC, underscoring the value of the PASS-01 Challenge.

Multi-modal digital twin model outperforms conventional biomarker stratification in pancreatic cancer

Better patient selection for treatment is critical to improving both cancer care and therapeutic development in oncology. The ability to predict individual patient responses to cancer treatment ahead of time would transform cancer care with substantial impact on outcomes, quality of life and cost. We generated molecula...

Developmental and MAPK-responsive transcription factors regulate distinct malignant cell states and associated genetic dependencies in pancreatic cancer

The authors apply ARACNe and metaVIPER to published scRNA-seq datasets to characterize pancreatic cancer subtypes, identifying six distinct cell states as well as their mechanistic determinants.