CDKN2A-inactivated pancreatic ductal adenocarcinoma exhibits therapeutic sensitivity to paclitaxel: A bioinformatics study

Jiunn Chang Lin, Tsang Pai Liu, Pei Ming Yang

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

The mutation of cyclin dependent kinase inhibitor 2A (CDKN2A) is frequently found in pancreatic ductal adenocarcinoma (PDAC). However, its prognostic and therapeutic roles in PDAC have not been extensively investigated yet. In this study, we mined and integrated the cancer genomics and chemogenomics data to investigate the roles of CDKN2A genetic alterations in PDAC patients’ prognosis and treatment. We found that functional CDKN2A inactivation caused by mutations and deep deletions predicted poor prognosis in PDAC patients. CDKN2A inactivation was associated with the upregulation of genes related to estrogen response, which can be overcome by CDKN2A restoration. Chemosensitivity profiling of PDAC cell lines and patient-derived organoids found that CDKN2A inactivation was associated with the increased sensitivity to paclitaxel and SN-38 (the active metabolite of irinotecan). However, only paclitaxel can mimic the effect of CDKN2A restoration, and its drug sensitivity was correlated with genes related to estrogen response. Therefore, our study suggested that CDKN2A-inactivated PDAC patients could benefit from the precision treatment with paclitaxel, whose albumin-stabilized nanoparticle formulation (nab-paclitaxel) has been approved for treating PDAC.

Original languageEnglish
Article number4019
Pages (from-to)1-11
Number of pages11
JournalJournal of Clinical Medicine
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 2020

Keywords

  • Bioinformatics
  • CDKN2A
  • Cell cycle
  • Paclitaxel
  • Pancreatic ductal adenocarcinoma

ASJC Scopus subject areas

  • Medicine(all)

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