Henry Ford Pancreatic Cancer Center, Henry Ford Health System, Detroit, Michigan 48202, USA
Genes Dev. 2021 Oct 1;35(19-20):1325-1326. doi: 10.1101/gad.348971.121.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Virtually all PDAC harbors an oncogenic mutation in the KRAS gene, making it the prime target for therapy. Most previous attempts to inhibit KRAS directly have been disappointing, but recent success in targeting some KRAS mutants presages a new era in PDAC therapy. Models of PDAC have predicted that identifying KRAS inhibitor resistance mechanisms will be critical. In this issue of , Hou and colleagues (pp. 1327-1332) identify one such mechanism in which the deubiquitinase USP21 up-regulates the nutrient-scavenging process of macropinocytosis, rescuing PDAC cells from extinction.
胰腺导管腺癌 (PDAC) 是最致命的癌症之一。几乎所有 PDAC 都携带有致癌基因突变 KRAS，使其成为治疗的主要靶点。大多数直接抑制 KRAS 的先前尝试都令人失望，但最近靶向某些 KRAS 突变体的成功预示着 PDAC 治疗的新时代即将到来。PDAC 模型预测，确定 KRAS 抑制剂耐药机制将是关键。在本期 中，Hou 及其同事（第 1327-1332 页）在其中一种机制中发现了这样一种机制，去泛素化酶 USP21 上调了巨胞饮作用的营养摄取过程，使 PDAC 细胞免于灭绝。
