Mutations in key driver genes of pancreatic cancer:molecularly targeted therapies and other clinical implications

• 作者: Hai-feng Hu Zeng Ye Yi Qin Xiao-wu Xu Xian-jun Yu Qi-feng Zhuo Shun-rong Ji
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（11）
• 所属期刊栏目: Review Article
• 页码范围: 1725-1741
• 页数: 17页
• 语种: 英文

摘要

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers,with a minimal difference between its incidence rate and mortality rate.Advances in oncology over the past several decades have dramatically improved the overall survival of patients with multiple cancers due to the implementation of new techniques in early diagnosis,therapeutic drugs,and personalized therapy.However,pancreatic cancers remain recalcitrant,with a 5-year relative survival rate of ＜9％.The lack of measures for early diagnosis,strong resistance to chemotherapy,ineffective adjuvant chemotherapy and the unavailability of molecularly targeted therapy are responsible for the high mortality rate of this notorious disease.Genetically,PDAC progresses as a complex result of the activation of oncogenes and inactivation of tumor suppressors.Although next-generation sequencing has identified numerous new genetic alterations,their clinical implications remain unknown.Classically,oncogenic mutations in genes such as KRAS and loss-of-function mutations in tumor suppressors,such as TP53,CDNK2A,DPC4/SMAD4,and BRCA2,are frequently observed in PDAC.Currently,research on these key driver genes is still the main focus.Therefore,studies assessing the functions of these genes and their potential clinical implications are of paramount importance.In this review,we summarize the biological function of key driver genes and pharmaceutical targets in PDAC.In addition,we conclude the results of molecularly targeted therapies in clinical trials and discuss how to utilize these genetic alterations in further clinical practice.