背景：胰腺癌（PDAC）是治疗最具挑战性的癌症之一，新的全身性治疗近期生存率略有改善。在以体细胞和种系基因组改变为基础的个体化治疗中存在越来越多的兴趣。
目的：针对体细胞和种系改变的治疗数据的系统评价，以及它们在PDAC中的下游通路。
方法：使用PRISMA指南进行了系统的文献检索，包括2008年1月1日之后发表的相关结果。
结果：共纳入71项相关研究。我们确定了36项针对KRAS途径的研究，最常见的是MEK抑制剂治疗。确定了22项研究，这些研究评估了在DNA损伤修复基因中具有有害突变的患者中基于铂的化疗和PARP抑制剂，并显示出令人鼓舞的结果。在错配修复缺陷/微卫星不稳定的患者中，免疫疗法已显示出活性。
结论：来自转化和临床研究的证据为PDAC的基因组靶向治疗提供了一个令人兴奋的平台。铂和PARP抑制剂靶向BRCA的有效性和免疫疗法的微卫星不稳定性已经确立,尽管如此,缺乏针对常见驱动癌基因的证据，需要做很多工作。重要的是鉴定KRAS-野生型PDAC的亚组(约5%),其中存在可靶向机会的富集。
BACKGROUND: Pancreatic cancer (PDAC) is one of the most challenging cancers to treat with modest recent improvements in survival from new systemic therapies. There is growing interest in individualized therapy underpinned by somatic and germline genomic alterations.
OBJECTIVE: A systematic
review of data on therapies targeting somatic and germline alterations, and their downstream pathways in PDAC.
METHODS: A systematic literature search was conducted using PRISMA guidelines to include relevant results published after January 1, 2008.
RESULTS: A total of 71 relevant studies were included. We identified 36 studies targeting the KRAS-pathway, the most common being with MEK-inhibitor therapy. Twenty-two studies were identified that evaluated platinum-based chemotherapy and PARP inhibitors in patients with deleterious mutations in DNA damage repair genes and have shown encouraging results. Immunotherapy has demonstrated activity in patients with mismatch repair deficiency/microsatellite instability.
CONCLUSIONS: Evidence from translational and clinical research presents an exciting platform for genomic targeted therapy in PDAC. Validity for targeting BRCA with platinum and PARP inhibitors and microsatellite instability with immune therapy has been established, nonetheless, evidence for targeting the common driver oncogenes is lacking and much work is needed. Of importance is identifying the subgroup of KRAS -wild type PDAC (approximately 5%) where there is enrichment for targetable opportunities.
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