Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer-related mortality, and it is expected to play an even bigger part in cancer burden in the years to come. Despite concerted efforts from scientists and physicians, patients have experienced little improvement in survival over the past decades, possibly because of the non-specific nature of the tested treatment modalities. Recently, the discovery of potentially targetable molecular alterations has paved the way for the personalized treatment of PDAC. Indeed, the central piece in the molecular framework of PDAC is starting to be unveiled.KRASmutations are seen in 90% of PDACs, and multiple studies have demonstrated their pivotal role in pancreatic carcinogenesis. Recent investigations have shed light on the differences in prognosis as well as therapeutic implications of the differentKRASmutations and disentangled the relationship between KRAS and effectors of downstream and parallel signaling pathways. Additionally, the recognition of other mechanisms involving KRAS-mediated pathogenesis, such as KRAS dosing and allelic imbalance, has contributed to broadening the current knowledge regarding this molecular alteration. Finally, KRAS G12C inhibitors have been recently tested in patients with pancreatic cancer with relative success, and inhibitors of KRAS harboring other mutations are under clinical development. These drugs currently represent a true hope for a meaningful leap forward in this dreadful disease.
胰腺导管腺癌（PDAC）仍是癌症相关死亡的重要原因，预计在未来几年其癌症负担将进一步加重。尽管科学家和医生们付出了协同努力，但过去几十年患者的生存率改善甚微，这可能与现有治疗方式的非特异性有关。近年来，潜在可靶向分子改变的发现为PDAC的个体化治疗开辟了新途径。事实上，PDAC分子框架的核心部分正逐渐被揭示。KRAS突变见于90%的PDAC病例，多项研究已证实其在胰腺癌发生中的关键作用。最新研究阐明了不同KRAS突变在预后及治疗意义上的差异，并揭示了KRAS与下游及平行信号通路效应因子间的复杂关系。此外，对KRAS介导发病机制中其他环节（如KRAS剂量效应和等位基因失衡）的认知，进一步拓展了关于该分子改变的理论体系。近期KRAS G12C抑制剂在胰腺癌患者中取得相对成功的临床试验结果，而针对其他KRAS突变的抑制剂也正处于临床研发阶段。这些药物为这一致命疾病的实质性突破带来了真正的希望。
Targeting KRAS in Pancreatic Ductal Adenocarcinoma: The Long Road to Cure
肿瘤(癌症)患者之家