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

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer Pub Date : 2024-11-01 DOI:10.1016/j.bbcan.2024.189220

Hongjuan Yao , Liaoxin Luo , Rui Li , Yelin Zhao , Li Zhang , Milica Pešić , Lin Cai , Liang Li

{"title":"New insight into the role of SMAD4 mutation/deficiency in the prognosis and therapeutic resistance of pancreatic ductal adenocarcinomas","authors":"Hongjuan Yao , Liaoxin Luo , Rui Li , Yelin Zhao , Li Zhang , Milica Pešić , Lin Cai , Liang Li","doi":"10.1016/j.bbcan.2024.189220","DOIUrl":null,"url":null,"abstract":"<div><div>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. <em>SMAD4</em> gene alterations in ∼55 % of patients emphasize its key role in PDAC progression, metastasis, resistance and immunity. Despite extensive studies on the TGF-β/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.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189220"},"PeriodicalIF":9.7000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et biophysica acta. Reviews on cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0304419X24001513","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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 ∼55 % of patients emphasize its key role in PDAC progression, metastasis, resistance and immunity. Despite extensive studies on the TGF-β/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.

查看原文本刊更多论文

SMAD4突变/缺陷在胰腺导管腺癌的预后和耐药性中的作用的新见解。

胰腺导管腺癌（PDAC）患者由于诊断晚、化疗耐药性强、辅助化疗效果不佳、分子靶向治疗不可用以及肿瘤微环境（TME）的深远免疫抑制效应等原因，预后不良，治疗效果令人失望。有多种关键驱动蛋白，如 KRAS、TP53、PTEN 和 SMAD4，可能与 PDAC 病因有关。目前对其分子机制的了解仍然有限。在约 55% 的患者中，SMAD4 基因的改变强调了其在 PDAC 进展、转移、抵抗和免疫中的关键作用。尽管对 TGF-β/SMAD 通路进行了广泛研究，但 SMAD4 基因突变/缺失对 PDAC 预后和治疗的影响，尤其是其耐药机制，尚未得到阐明。本综述总结了 SMAD4 缺陷对 PDAC 患者预后和耐药性影响的最新进展。它可能是一个预测和预后的生物标志物或治疗靶点，以达到预期的临床疗效。此外，我们还讨论了根据 SMAD4 遗传状态实施靶向治疗的潜在策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biochimica et biophysica acta. Reviews on cancer 医学-生化与分子生物学

CiteScore

17.20

自引率

0.00%

发文量

138

审稿时长

33 days

期刊介绍： Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.