Review Mechanisms of PDAC subtype heterogeneity and therapy response

被引：39

作者：

Espinet, Elisa ^{[1
,2
]}

Klein, Lukas ^{[3
]}

Pure, Ellen ^{[4
]}

Singh, Shiv K. ^{[3
,5
]}

机构：

[1] Univ Barcelona UB, Sch Med, Dept Pathol & Expt Therapy, Barcelona, Spain

[2] Inst Invest Biomed Bellvitge IDIBELL, Mol Mech & Expt Therapy Oncol Program Oncobell, Barcelona, Spain

[3] Univ Med Ctr Gottingen, Dept Gastroenterol Gastrointestinal Oncol & Endoc, Gottingen, Germany

[4] Univ Penn, Dept Biomed Sci, Philadelphia, PA USA

[5] Univ Med Ctr GOttingen, Clin Res Unit 5002, KFO5002, Gottingen, Germany

来源：

TRENDS IN CANCER | 2022年 / 8卷 / 12期

关键词：

FIBROBLAST HETEROGENEITY; TUMOR; CELL; IDENTIFICATION; DEFINE; GROWTH; DIFFERENTIATION; ADENOCARCINOMA; ENVIRONMENT; POPULATIONS;

D O I：

10.1016/j.trecan.2022.08.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pancreatic ductal adenocarcinoma (PDAC) is clinically challenging due to late diagnosis and resistance to therapy. Two major PDAC subtypes have been defined based on malignant epithelial cell gene expression profiles; the basal-like/squamous subtype is associated with a worse prognosis and therapeutic resistance as opposed to the classical subtype. Subtype specification is not binary, consistent with plasticity of malignant cell phenotype. PDAC heterogeneity and plasticity reflect partly malignant cell-intrinsic transcriptional and epigenetic regulation. However, the stromal and immune compartments of the tumor micro -environment (TME) also determine disease progression and therapy response. It is evident that integration of intrinsic and extrinsic factors can dictate subtype heterogeneity, and thus, delineating the pathways involved can help to reprogram PDAC towards a classical/druggable subtype.

引用

页码：1060 / 1071

页数：12

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