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针对 miRNA 并将其用作潜在的治疗选择,以绕过胰腺导管腺癌的耐药性。

Targeting miRNA and using miRNA as potential therapeutic options to bypass resistance in pancreatic ductal adenocarcinoma.

机构信息

Department of Medical Oncology, Amsterdam UMC, location VUMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands.

Cancer Pharmacology Lab, Fondazione Pisana per La Scienza, Pisa, Italy.

出版信息

Cancer Metastasis Rev. 2023 Sep;42(3):725-740. doi: 10.1007/s10555-023-10127-w. Epub 2023 Jul 25.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with poor prognosis due to early metastasis, low diagnostic rates at early stages, and resistance to current therapeutic regimens. Despite numerous studies and clinical trials, the mortality rate for PDAC has shown limited improvement. Therefore, there is a pressing need to attain. a more comprehensive molecular characterization to identify biomarkers enabling early detection and evaluation of treatment response. MicroRNA (miRNAs) are critical regulators of gene expression on the post-transcriptional level, and seem particularly interesting as biomarkers due to their relative stability, and the ability to detect them in fixed tissue specimens and biofluids. Deregulation of miRNAs is common and affects several hallmarks of cancer and contribute to the oncogenesis and metastasis of PDAC. Unique combinations of upregulated oncogenic miRNAs (oncomiRs) and downregulated tumor suppressor miRNAs (TsmiRs), promote metastasis, characterize the tumor and interfere with chemosensitivity of PDAC cells. Here, we review several oncomiRs and TsmiRs involved in chemoresistance to gemcitabine and FOLFIRINOX in PDAC and highlighted successful/effective miRNA-based therapy approaches in vivo. Integrating miRNAs in PDAC treatment represents a promising therapeutic avenue that can be used as guidance for personalized medicine for PDAC patients.

摘要

胰腺导管腺癌(PDAC)是一种高度侵袭性疾病,预后不良,原因是早期转移、早期诊断率低以及对当前治疗方案的耐药性。尽管进行了大量的研究和临床试验,但 PDAC 的死亡率改善有限。因此,迫切需要获得更全面的分子特征,以识别能够早期检测和评估治疗反应的生物标志物。microRNA(miRNA)是转录后水平基因表达的关键调节因子,由于其相对稳定性以及在固定组织标本和生物体液中检测它们的能力,它们作为生物标志物特别有趣。miRNA 的失调很常见,会影响癌症的几个标志,并有助于 PDAC 的肿瘤发生和转移。上调的致癌 miRNA(oncomiRs)和下调的肿瘤抑制 miRNA(TsmiRs)的独特组合促进转移、表征肿瘤并干扰 PDAC 细胞的化疗敏感性。在这里,我们回顾了几种参与 PDAC 对吉西他滨和 FOLFIRINOX 化疗耐药的 oncomiRs 和 TsmiRs,并强调了 miRNA 为基础的治疗方法在体内的成功/有效性。将 miRNAs 整合到 PDAC 治疗中代表了一种很有前途的治疗途径,可以作为 PDAC 患者个性化医学的指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e85a/10584721/0854cc33aeeb/10555_2023_10127_Fig1_HTML.jpg

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