Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
Pharmaceutics, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, the Netherlands.
Theranostics. 2021 Aug 25;11(18):9022-9037. doi: 10.7150/thno.60350. eCollection 2021.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of cancer due to the relatively late diagnosis and the limited therapeutic options. Current treatment regimens mainly comprise the cytotoxic agents gemcitabine and FOLFIRINOX. These compounds have shown limited efficacy and severe side effects, highlighting the necessity for earlier detection and the development of more effective, and better-tolerated treatments. Although targeted therapies are promising for the treatment of several types of cancer, identification of suitable targets for early diagnosis and targeted therapy of PDAC is challenging. Interestingly, several transmembrane proteins are overexpressed in PDAC cells that show low expression in healthy pancreas and may therefore serve as potential targets for treatment and/or diagnostic purposes. In this review we describe the 11 most promising transmembrane proteins, carefully selected after a thorough literature search. Favorable features and potential applications of each target, as well as the results of the preclinical and clinical studies conducted in the past ten years, are discussed in detail.
胰腺导管腺癌(PDAC)是最致命的癌症类型之一,这主要是由于相对较晚的诊断和有限的治疗选择。目前的治疗方案主要包括细胞毒性药物吉西他滨和 FOLFIRINOX。这些化合物的疗效有限,副作用严重,这突出表明需要更早的检测和开发更有效和耐受性更好的治疗方法。尽管靶向治疗对治疗几种类型的癌症具有广阔的前景,但确定适合 PDAC 的早期诊断和靶向治疗的合适靶点仍然具有挑战性。有趣的是,几种跨膜蛋白在 PDAC 细胞中过度表达,而在健康胰腺中表达水平较低,因此它们可能成为治疗和/或诊断目的的潜在靶点。在本综述中,我们描述了 11 种最有前途的跨膜蛋白,这些蛋白是在经过彻底的文献检索后精心挑选的。详细讨论了每个靶标的有利特征和潜在应用,以及过去十年进行的临床前和临床研究的结果。