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Splicing dysregulation: hallmark and therapeutic opportunity in pancreatic cancer

Chiara Naro1, Veronica Ruta2, Claudio Sette1

  • 1Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart, 00168 Rome, Italy; Gemelli Science and Technology Park (GSTeP) Organoids Research Core Facility, Fondazione Policlinico A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy.

Trends in Molecular Medicine
|December 8, 2024
PubMed

Insights

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer. Targeting its splicing dysregulation offers a promising new therapeutic strategy for this difficult-to-treat disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis, often diagnosed late.
  • Current treatments for PDAC are limited by chemoresistance and a lack of effective targeted therapies.
  • Aberrant gene splicing is increasingly recognized as a critical factor in PDAC development and progression.

Purpose of the Study:

  • To review the evidence linking splicing dysregulation to pancreatic cancer.
  • To explore the potential of targeting splicing as a therapeutic strategy for PDAC.
  • To highlight cancer-specific vulnerabilities arising from altered splicing.

Main Methods:

  • Review of existing scientific literature and research findings on splicing in PDAC.
  • Analysis of the role of deregulated splicing factors in tumorigenesis.
  • Discussion of therapeutic opportunities presented by targeting splicing pathways.

Main Results:

  • Splicing factor deregulation is a hallmark of PDAC, contributing to various stages of cancer.
  • Altered splicing impacts PDAC from initial inflammation to metastasis and chemoresistance.
  • Splicing dysregulation represents a potential vulnerability exploitable for targeted therapy.

Conclusions:

  • Splicing plays a crucial role in the pathogenesis of pancreatic ductal adenocarcinoma.
  • Targeting aberrant splicing mechanisms presents a promising avenue for novel PDAC therapies.
  • Further research into splicing dysregulation could unlock effective treatments for this devastating cancer.
Keywords:
drug resistanceimmunotherapymolecular phenotypepancreatic cancersplicing

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