Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates.
Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.
Int J Mol Sci. 2021 Sep 23;22(19):10219. doi: 10.3390/ijms221910219.
The most frequent mutated oncogene family in the history of human cancer is the RAS gene family, including , , and, most importantly, . A hallmark of pancreatic cancer, recalcitrant cancer with a very low survival rate, is the prevalence of oncogenic mutations in the gene. Due to this fact, studying the function of and the impact of its mutations on the tumor microenvironment (TME) is a priority for understanding pancreatic cancer progression and designing novel therapeutic strategies for the treatment of the dismal disease. Despite some recent enlightening studies, there is still a wide gap in our knowledge regarding the impact of mutations on different components of the pancreatic TME. In this review, we will present an updated summary of mutant role in the initiation, progression, and modulation of the TME of pancreatic ductal adenocarcinoma (PDAC). This review will highlight the intriguing link between diabetes mellitus and PDAC, as well as vitamin D as an adjuvant effective therapy via TME modulation of PDAC. We will also discuss different ongoing clinical trials that use oncogene signaling network as therapeutic targets.
在人类癌症史上，最常见的突变致癌基因家族是 RAS 基因家族，包括 、 、 和 ，其中最重要的是 。胰腺癌是一种难治性癌症，存活率非常低，其标志性特征是 基因中存在致癌突变。由于这一事实，研究 基因的功能及其突变对肿瘤微环境（TME）的影响是理解胰腺癌进展和设计治疗这种可怕疾病的新治疗策略的优先事项。尽管最近有一些启发性的研究，但我们对于 突变对胰腺 TME 的不同成分的影响的认识仍存在很大差距。在这篇综述中，我们将对突变 基因在胰腺导管腺癌（PDAC）的 TME 的起始、进展和调节中的作用进行最新总结。这篇综述将强调糖尿病与 PDAC 之间的有趣联系，以及维生素 D 通过调节 PDAC 的 TME 作为一种有效的辅助治疗方法。我们还将讨论正在进行的临床试验，这些试验将 致癌基因信号网络作为治疗靶点。
