Emelyanova Marina, Pudova Elena, Khomich Darya, Krasnov George, Popova Anna, Abramov Ivan, Mikhailovich Vladimir, Filipenko Maxim, Menshikova Sofia, Tjulandin Sergey, Pokataev Ilya
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russian Federation.
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation.
Ther Adv Med Oncol. 2022 Mar 15;14:17588359221083050. doi: 10.1177/17588359221083050. eCollection 2022.
Mutations in homologous recombination (HR) and Fanconi anemia (FA) genes may predispose to pancreatic cancer (PC) and enable the prediction of sensitivity to platinum-based chemotherapy. FOLFIRINOX is a standard treatment option for non-selected PC patients and could be effective due to undiagnosed DNA repair deficiency. Here, we aimed to determine the frequency of mutations in genes involved in the HR and FA pathways, evaluate their clinical implications, and determine the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of PC patients treated with platinum.
We performed targeted DNA sequencing of 30 genes (, , , , , , , , , , , , , , , , , , , , , , , , , , , , , and ) for 543 PC patients.
In -mutated patients with advanced PC (33 patients, 6.1%), the PFS and OS were higher for first-line platinum therapy than for non-platinum therapy [PFS: HR = 0.28, 95% confidence interval (CI) = 0.10-0.81, = 0.02; OS: HR = 0.31, 95% CI = 0.08-1.16, = 0.08]. Among 93 patients (17.1%) with mutations in other HR/FA genes, no statistically significant difference in PFS and OS was observed between first-line platinum therapy and non-platinum therapy (PFS: HR = 0.83, 95% CI = 0.43-1.62, = 0.59; OS: HR = 0.58, 95% CI = 0.28-1.22, = 0.15). For patients with early PC, no prognostic value was observed for , , or other HR/FA genes mutations. Moreover, a personal history of breast, ovarian, pancreatic, or prostate cancer was identified as the only independent predictor of the risk of mutations (HR = 5.83, 95% CI = 2.16-15.73, < 0.01).
Mutations in the and genes increase the sensitivity of PC to platinum agents. Thus, alterations in these genes in PC patients must be determined prior to anticancer therapy.
同源重组（HR）和范可尼贫血（FA）基因的突变可能使患者易患胰腺癌（PC），并有助于预测对铂类化疗的敏感性。FOLFIRINOX是未筛选的PC患者的标准治疗选择，由于未诊断出的DNA修复缺陷，该治疗可能有效。在此，我们旨在确定HR和FA途径相关基因的突变频率，评估其临床意义，并确定接受铂类治疗的PC患者的客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。
我们对543例PC患者的30个基因（，，，，，，，，，，，，，，，，，，，，，，，，，，，，，和）进行了靶向DNA测序。
在携带突变的晚期PC患者（33例，6.1%）中，一线铂类治疗的PFS和OS高于非铂类治疗[PFS：风险比（HR）=0.28，95%置信区间（CI）=0.10-0.81，=0.02；OS：HR=0.31，95%CI=0.08-1.16，=0.08]。在93例（17.1%）其他HR/FA基因突变的患者中，一线铂类治疗和非铂类治疗的PFS和OS未观察到统计学显著差异（PFS：HR=0.83，95%CI=0.43-1.62，=0.59；OS：HR=0.58，95%CI=0.28-1.22，=0.15）。对于早期PC患者，、或其他HR/FA基因突变未观察到预后价值。此外，乳腺癌、卵巢癌、胰腺癌或前列腺癌的个人病史被确定为突变风险的唯一独立预测因素（HR=5.83，95%CI=2.16-15.73，<0.01）。
和基因的突变增加了PC对铂类药物的敏感性。因此，在抗癌治疗前必须确定PC患者这些基因的改变情况。
