Dardare Julie, Witz Andréa, Merlin Jean-Louis, Bochnakian Agathe, Toussaint Paul, Gilson Pauline, Harlé Alexandre
Université de Lorraine, CNRS UMR7039 CRAN, Service de Biopathologie, Institut de Cancérologie de Lorraine, 54519 Vandoeuvre-lès-Nancy, France.
Pharmaceuticals (Basel). 2021 Jul 29;14(8):740. doi: 10.3390/ph14080740.
Pancreatic ductal adenocarcinoma (PDAC) is one of the malignancies with the worst prognosis despite a decade of efforts. Up to eighty percent of patients are managed at late stages with metastatic disease, in part due to a lack of diagnosis. The effectiveness of PDAC therapies is challenged by the early and widespread metastasis. Epithelial to mesenchymal transition (EMT) is a major driver of cancer progression and metastasis. This process allows cancer cells to gain invasive properties by switching their phenotype from epithelial to mesenchymal. The importance of EMT has been largely described in PDAC, and its importance is notably highlighted by the two major subtypes found in PDAC: the classical epithelial and the quasi-mesenchymal subtypes. Quasi-mesenchymal subtypes have been associated with a poorer prognosis. EMT has also been associated with resistance to treatments such as chemotherapy and immunotherapy. EMT is associated with several key molecular markers both epithelial and mesenchymal. Those markers might be helpful as a biomarker in PDAC diagnosis. EMT might becoming a key new target of interest for the treatment PDAC. In this review, we describe the role of EMT in PDAC, its contribution in diagnosis, in the orientation and treatment follow-up. We also discuss the putative role of EMT as a new therapeutic target in the management of PDAC.
尽管经过了十年的努力,胰腺导管腺癌(PDAC)仍是预后最差的恶性肿瘤之一。高达80%的患者在疾病晚期出现转移,部分原因是缺乏诊断。PDAC治疗的有效性受到早期广泛转移的挑战。上皮-间质转化(EMT)是癌症进展和转移的主要驱动因素。这个过程使癌细胞通过将其表型从上皮细胞转变为间充质细胞而获得侵袭性。EMT在PDAC中的重要性已得到大量描述,PDAC中发现的两种主要亚型——经典上皮亚型和准间充质亚型尤其突出了其重要性。准间充质亚型与较差的预后相关。EMT还与化疗和免疫治疗等治疗的耐药性有关。EMT与上皮和间充质的几个关键分子标志物相关。这些标志物可能有助于作为PDAC诊断的生物标志物。EMT可能成为PDAC治疗的一个关键新靶点。在这篇综述中,我们描述了EMT在PDAC中的作用,其在诊断、治疗方向和随访中的贡献。我们还讨论了EMT作为PDAC治疗新靶点的潜在作用。