KRAS wild-type pancreatic ductal adenocarcinoma: molecular pathology and therapeutic opportunities.
KRAS wild-type pancreatic ductal adenocarcinoma: molecular pathology and therapeutic opportunities.
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DOI：
10.1186/s13046-020-01732-6
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发表时间：
2020-10-28
期刊：
影响因子：
--
通讯作者：
Scarpa A
中科院分区：
文献类型：
--
作者：
Luchini C;Paolino G;Mattiolo P;Piredda ML;Cavaliere A;Gaule M;Melisi D;Salvia R;Malleo G;Shin JI;Cargnin S;Terrazzino S;Lawlor RT;Milella M;Scarpa A
胰腺导管腺癌（Pancreatic ductal adenocarcinoma， PDAC）是一种致死性疾病，其主要分子特征是KRAS突变导致MAPK通路激活，90%的病例存在这种突变。KRAS野生型PDAC的遗传景观可分为三类。第一种是由于BRAF突变导致MAPK通路激活的肿瘤，发生率高达4%。第二种包括由于DNA错配修复缺陷（dMMR）导致的微卫星不稳定性（MSI）肿瘤，这种情况约占2%，也具有很高的肿瘤突变负担。第三类是含有激酶融合基因的肿瘤，约占病例的4%。虽然KRAS的治疗性分子靶向是一个尚未解决的挑战，但KRAS野生型pdac有潜在的定制治疗选择，包括第一组使用BRAF拮抗剂和MAPK抑制剂，MSI/dMMR组使用抗pd -1/PD-L1药物进行免疫治疗，第三组使用激酶抑制剂。这就需要补充PDAC的组织学诊断，常规测定KRAS，然后对KRAS阴性病例进行全面的分子谱分析。
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease, whose main molecular trait is the MAPK pathway activation due to KRAS mutation, which is present in 90% of cases. The genetic landscape of KRAS wild type PDAC can be divided into three categories. The first is represented by tumors with an activated MAPK pathway due to BRAF mutation that occur in up to 4% of cases. The second includes tumors with microsatellite instability (MSI) due to defective DNA mismatch repair (dMMR), which occurs in about 2% of cases, also featuring a high tumor mutational burden. The third category is represented by tumors with kinase fusion genes, which marks about 4% of cases. While therapeutic molecular targeting of KRAS is an unresolved challenge, KRAS-wild type PDACs have potential options for tailored treatments, including BRAF antagonists and MAPK inhibitors for the first group, immunotherapy with anti-PD-1/PD-L1 agents for the MSI/dMMR group, and kinase inhibitors for the third group. This calls for a complementation of the histological diagnosis of PDAC with a routine determination of KRAS followed by a comprehensive molecular profiling of KRAS-negative cases.
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DOI：
10.1158/1078-0432.ccr-17-3099
发表时间：
2018-03-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hu ZI;Shia J;Stadler ZK;Varghese AM;Capanu M;Salo-Mullen E;Lowery MA;Diaz LA Jr;Mandelker D;Yu KH;Zervoudakis A;Kelsen DP;Iacobuzio-Donahue CA;Klimstra DS;Saltz LB;Sahin IH;O'Reilly EM
通讯作者：
O'Reilly EM
影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
影响因子：
28.2
作者：
Chmielecki, Juliann;Hutchinson, Katherine E.;Stephens, Philip J.
通讯作者：
Stephens, Philip J.
影响因子：
29.4
作者：
Humphris, Jeremy L.;Patch, Ann-Marie;Biankin, Andrew V.
通讯作者：
Biankin, Andrew V.
影响因子：
11.5
作者：
Jones, Martin R.;Williamson, Laura M.;Renouf, Daniel J.
通讯作者：
Renouf, Daniel J.