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

Jiunn Chang Lin, Tsang Pai Liu, Pei Ming Yang

研究成果: 雜誌貢獻文章同行評審

12 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
文章編號4019
頁(從 - 到)1-11
頁數11
期刊Journal of Clinical Medicine
9
發行號12
DOIs
出版狀態已發佈 - 12月 2020

ASJC Scopus subject areas

  • 醫藥 (全部)

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