Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most formidable challenges in oncology, characterized by its late detection and poor prognosis. Artificial intelligence (AI) and machine learning (ML) are emerging as pivotal tools in revolutionizing PDAC care across various dimensions. Consequently, many studies have focused on using AI to improve the standard of PDAC care. This review article attempts to consolidate the literature from the past five years to identify high-impact, novel, and meaningful studies focusing on their transformative potential in PDAC management. Our analysis spans a broad spectrum of applications, including but not limited to patient risk stratification, early detection, and prediction of treatment outcomes, thereby highlighting AI’s potential role in enhancing the quality and precision of PDAC care. By categorizing the literature into discrete sections reflective of a patient’s journey from screening and diagnosis through treatment and survivorship, this review offers a comprehensive examination of AI-driven methodologies in addressing the multifaceted challenges of PDAC. Each study is summarized by explaining the dataset, ML model, evaluation metrics, and impact the study has on improving PDAC-related outcomes. We also discuss prevailing obstacles and limitations inherent in the application of AI within the PDAC context, offering insightful perspectives on potential future directions and innovations.

Prognostic markers such as overall survival (OS) and tertiary lymphoid structure (TLS) ratios, alongside diagnostic signatures like primary cancer-type classification, provide critical information for treatment selection, risk stratification, and longitudinal care planning across the oncology continuum. However, extracting these signals solely from sparse, high-dimensional multi-omics data remains a major challenge due to heterogeneity and frequent missingness in patient profiles. To address this challenge, we present SeNMo, a self-normalizing deep neural network trained on five heterogeneous omics layers—gene expression, DNA methylation, miRNA abundance, somatic mutations, and protein expression—along with the clinical variables, that learns a unified representation robust to missing modalities. Trained on more than 10,000 patient profiles across 32 tumor types from The Cancer Genome Atlas (TCGA), SeNMo provides a baseline that can be readily fine-tuned for diverse downstream tasks. On a held-out TCGA test set, the model achieved a concordance index of 0.758 for OS prediction, while external evaluation yielded 0.73 on the CPTAC lung squamous cell carcinoma cohort and 0.66 on an independent 108-patient Moffitt Cancer Center cohort. Furthermore, on Moffitt’s cohort, baseline SeNMo fine-tuned for TLS ratio prediction aligned with expert annotations (p < 0.05) and sharply separated high- versus low-TLS groups, reflecting distinct survival outcomes. Without altering the backbone, a single linear head classified primary cancer type with 99.8% accuracy across the 33 classes. By unifying diagnostic and prognostic predictions in a modality-robust architecture, SeNMo demonstrated strong performance across multiple clinically relevant tasks, including survival estimation, cancer classification, and TLS ratio prediction, highlighting its translational potential for multi-omics oncology applications.

Investigating multi-omics data is crucial for unraveling the complex biological mechanisms underlying cancer, thereby enabling effective strategies for prevention, early detection, diagnosis, and treatment. However, predicting patient outcomes through the integration of all available multi-omics data remains an understudied topic. We present SeNMo, a self-normalizing deep neural network trained on multi-omics data across 33 cancer types. SeNMo is particularly efficient in handling multi-omics data characterized by high-width (many features) and low-length (fewer samples) attributes. We trained SeNMo for predicting overall survival of patients using pan-cancer multi-omics data involving 33 cancer sites from the publicly available NCI Genomics Data Commons. The multi-omics data includes gene expression, DNA methylation, miRNA expression, DNA mutations, protein expression modalities, and clinical data. SeNMo was validated on two independent cohorts: Moffitt Cancer Center and CPTAC lung squamous cell carcinoma. The baseline model, trained to predict overall survival, achieved a concordance index (C-Index) of 0.76 in the validation regime and 0.758 on the held-out test set. Furthermore, the model demonstrated strong generalizability, achieving an average accuracy of 99.8% in predicting primary cancer type across pan-cancer cohort. SeNMo further demonstrated significant performance (p< 0.05) in predicting tertiary lymph structures from multi-omics data, showing generalizability across cancer types, molecular data types, and clinical endpoints. SeNMo and similar models are poised to transform the oncology landscape, offering hope for more effective, efficient, and personalized cancer care.