Molecular Therapeutics of Pancreatic Ductal Adenocarcinoma: Targeted Pathways and the Role of Cancer Stem Cells

被引：27

作者：

Stoica, Andrei-Florian ^{[1
]}

Chang, Chao-Hui ^{[1
]}

Pauklin, Siim ^{[1
]}

机构：

[1] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Botnar Res Ctr, Old Rd, Oxford OX3 7LD, England

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2020年 / 41卷 / 12期

基金：

英国工程与自然科学研究理事会;

关键词：

NAB-PACLITAXEL; BROMODOMAIN INHIBITORS; METASTATIC ACTIVITY; SIGNALING PATHWAYS; TUMOR-GROWTH; PHASE-II; GEMCITABINE; KRAS; IDENTIFICATION; STROMA;

D O I：

10.1016/j.tips.2020.09.008

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in humans due to late detection and highly metastatic characteristics. PDAC cells vary in their tumorigenic capabilities with the presence of a subset of PDAC cells known as pancreatic cancer stem cells (CSCs), which are more resistant to currently used therapeutics. Here, we describe the role of CSCs and tumour stroma in developing therapeutic strategies for PDAC and suggest that developmental plasticity could be considered a hallmark of cancers. We provide an overview of the molecular targets in PDAC treatments, including targeted therapies of cellular processes such as proliferation, evasion of growth suppressors, activating metastasis, and metabolic effects. Since PDAC is an inflammation driven cancer, we also revisit therapeutic strategies targeting inflammation and immunotherapy. Lastly, we suggest that targeting epigenetic mechanisms opens therapeutic routes for heterogeneous cancer cell populations, including CSCs.

引用

页码：977 / 993

页数：17

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