Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Semin Cancer Biol. 2022 Nov;86(Pt 2):28-45. doi: 10.1016/j.semcancer.2022.08.011. Epub 2022 Sep 1.
Transcription factors (TFs) are essential for proper activation of gene during the process of organogenesis, differentiation, lineage specificity. Reactivation or dysregulation of TFs regulatory networks could lead to deformation of organs, diseases including various malignancies. Currently, understanding the mechanism of oncogenesis became a necessity for the development of targeted therapeutic strategy for different cancer types. It is evident that many TFs go awry in cancers of the pancreas such as pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine neoplasms (PanNENs). These mutated or dysregulated TFs abnormally controls various signaling pathways in PDAC and PanNENs including RTK, PI3K-PTEN-AKT-mTOR, JNK, TGF-β/SMAD, WNT/β-catenin, SHH, NOTCH and VEGF which in turn regulate different hallmarks of cancer. Aberrant regulation of such pathways have been linked to the initiation, progression, metastasis, and resistance in pancreatic cancer. As of today, a number of TFs has been identified as crucial regulators of pancreatic cancer and a handful of them shown to have potential as therapeutic targets in pre-clinical and clinical settings. In this review, we have summarized the current knowledge on the role and therapeutic usefulness of TFs in PDAC and PanNENs.
转录因子 (TFs) 在器官发生、分化和谱系特异性过程中对于基因的正确激活至关重要。TFs 调控网络的重新激活或失调可能导致器官变形,引发各种恶性肿瘤等疾病。目前,了解致癌机制对于开发针对不同癌症类型的靶向治疗策略变得非常必要。很明显,许多 TFs 在胰腺导管腺癌 (PDAC) 和胰腺神经内分泌肿瘤 (PanNENs) 等胰腺癌症中出现异常。这些突变或失调的 TFs 异常控制着 PDAC 和 PanNENs 中的各种信号通路,包括 RTK、PI3K-PTEN-AKT-mTOR、JNK、TGF-β/SMAD、WNT/β-catenin、SHH、NOTCH 和 VEGF,这些信号通路反过来又调节癌症的不同特征。这些通路的异常调节与胰腺癌的发生、进展、转移和耐药性有关。截至目前,已经确定了许多 TFs 作为胰腺癌的关键调控因子,其中一些已经在临床前和临床环境中显示出作为治疗靶点的潜力。在这篇综述中,我们总结了 TFs 在 PDAC 和 PanNENs 中的作用和治疗用途的最新知识。