New insight into the role of SMAD4 mutation/deficiency in the prognosis and therapeutic resistance of pancreatic ductal adenocarcinomas

被引：4

作者：

Yao, Hongjuan ^{[1
]}

Luo, Liaoxin ^{[2
]}

Li, Rui ^{[1
]}

Zhao, Yelin ^{[1
]}

Zhang, Li ^{[1
]}

Pesic, Milica ^{[3
]}

Cai, Lin ^{[2
]}

Li, Liang ^{[1
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll CAMS, Inst Med Biotechnol, State Key Lab Resp Hlth & Multimorbid, NHC Key Lab Biotechnol Microbial Drugs,Dept Oncol, 1 Tiantan Xili, Beijing 100050, Peoples R China

[2] Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325000, Peoples R China

[3] Univ Belgrade, Dept Neurobiol, Natl Inst Republ Serbia, Inst Biol Res Sinisa Stankovic, Despota Stefana 142, Belgrade 11060, Serbia

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER | 2024年 / 1879卷 / 06期

关键词：

SMAD4; mutation/deficiency; Pancreatic ductal adenocarcinoma (PDAC); Prognosis; Therapeutic resistance; Clinical implementation; TGF-BETA; DOWN-REGULATION; COLON-CANCER; IN-VITRO; MESENCHYMAL TRANSITION; TUMOR MICROENVIRONMENT; DRUG-RESISTANCE; IMMUNE EVASION; POOR-PROGNOSIS; CELL-GROWTH;

D O I：

10.1016/j.bbcan.2024.189220

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pancreatic ductal adenocarcinoma (PDAC) patients have an unfavorable prognosis and disappointing treatment outcomes because of late diagnosis, high chemotherapy resistance, ineffective adjuvant chemotherapy, unavailable molecular targeted therapy, and profound immunosuppressive effects in the tumor microenvironment (TME). There are a variety of critical driver proteins, such as KRAS, TP53, PTEN and SMAD4, putatively involved in PDAC etiology. Current knowledge of their molecular mechanisms is still limited. SMAD4 gene alterations in similar to 55 % of patients emphasize its key role in PDAC progression, metastasis, resistance and immunity. Despite extensive studies on the TGF-beta/SMAD pathway, the impact of SMAD4 mutation/deficiency on PDAC prognosis and treatment, especially its mechanism in drug resistance, has not yet been elucidated. This review summarizes the latest advances in the effect of SMAD4 deficiency on the prognosis and therapeutic resistance of PDAC patients. It might be a predictive and prognostic biomarker or therapeutic target to achieve the desired clinical benefits. Moreover, we discuss potential strategies to implement targeted therapies in terms of SMAD4 genetic status.

引用

页数：12

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