Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine

被引：67

作者：

Conway, James R. W. ^{[1
,2
]}

Herrmann, David ^{[1
,2
,3
]}

Evans, T. R. Jeffry ^{[4
,5
]}

Morton, Jennifer P. ^{[4
,5
]}

Timpson, Paul ^{[1
,2
,3
]}

机构：

[1] Garvan Inst Med Res, Sydney, NSW, Australia

[2] Kinghorn Canc Ctr, Canc Div, Sydney, NSW, Australia

[3] Univ New South Wales, St Vincents Clin Sch, Fac Med, Sydney, NSW, Australia

[4] Canc Res UK Beatson Inst, Canc Dept, Glasgow, Lanark, Scotland

[5] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland

来源：

GUT | 2019年 / 68卷 / 04期

基金：

澳大利亚国家健康与医学研究理事会; 澳大利亚研究理事会;

关键词：

EPIDERMAL-GROWTH-FACTOR; ADVANCED SOLID TUMORS; PHASE-I TRIAL; PAPILLARY MUCINOUS NEOPLASMS; RENAL-CELL CARCINOMA; ORAL MEK INHIBITOR; FACTOR RECEPTOR; BREAST-CANCER; MUTANT P53; INTRAEPITHELIAL NEOPLASIA;

D O I：

10.1136/gutjnl-2018-316822

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Pancreatic ductal adenocarcinoma (PDAC) is among the most deadly solid tumours. This is due to a generally late-stage diagnosis of a primarily treatment-refractory disease. Several large-scale sequencing and mass spectrometry approaches have identified key drivers of this disease and in doing so highlighted the vast heterogeneity of lower frequency mutations that make clinical trials of targeted agents in unselected patients increasingly futile. There is a clear need for improved biomarkers to guide effective targeted therapies, with biomarker-driven clinical trials for personalised medicine becoming increasingly common in several cancers. Interestingly, many of the aberrant signalling pathways in PDAC rely on downstream signal transduction through the mitogen-activated protein kinase and phosphoinositide 3-kinase (PI3K) pathways, which has led to the development of several approaches to target these key regulators, primarily as combination therapies. The following review discusses the trend of PDAC therapy towards molecular subtyping for biomarker-driven personalised therapies, highlighting the key pathways under investigation and their relationship to the PI3K pathway.

引用

页码：742 / +

页数：17

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