Publication details
Beyond the genome: alternative splicing as a key driver of cellular plasticity and clinical heterogeneity in pancreatic cancer.
| Authors | |
|---|---|
| Year of publication | 2026 |
| Type | Peer-reviewed scientific article |
| Magazine / Source | CLINICAL AND EXPERIMENTAL MEDICINE |
| MU Faculty or unit | |
| Citation | |
| web | https://rdcu.be/G4rZq4exYAma |
| Doi | https://doi.org/10.1007/s10238-026-02308-y |
| Description | Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with an exceptionally poor prognosis, characterized by a relatively stable and recurrent spectrum of driver mutations that fail to fully explain the clinical heterogeneity of the disease. In this review, we evaluate alternative splicing (AS) as an additional regulatory layer underlying tumor plasticity and adaptive rewiring. We provide a mechanistically integrated overview of AS dysregulation in PDAC, including the contributions of specialized bioinformatic resources and databases such as TCGASpliceSeq, OncoSplicing, and MAJIQlopedia. We discuss how dysregulation of splicing factors, particularly from the SR and hnRNP protein families, acts as an upstream regulator reprogramming the isoform landscape. Furthermore, we examine how AS deregulation functionally contributes to key hallmarks of malignancy, including apoptosis resistance, metabolic adaptation, and metastatic plasticity. Then, we critically address the methodological aspects of isoform identification and outline future research directions, emphasizing the need for protein-level validation and the translational potential of therapeutic strategies, such as antisense oligonucleotides or spliceosome inhibitors. In conclusion, this review establishes that AS represents a biologically important and potentially ACCEPTED MANUSCRIPTARTICLE IN PRESSARTICLE IN PRESS therapeutically exploitable dimension of PDAC molecular biology, extending classical genetic models of tumor pathogenesis. |
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