Landscape of Combination Immunotherapy and Targeted Therapy to Improve Cancer Management.
Landscape of Combination Immunotherapy and Targeted Therapy to Improve Cancer Management.
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联合免疫疗法和靶向治疗改善癌症管理的前景。
DOI：
10.1158/0008-5472.can-16-3338
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发表时间：
2017-07-01
期刊：
影响因子：
11.2
通讯作者：
Chanock SJ
中科院分区：
文献类型：
--
作者：
Colli LM;Machiela MJ;Zhang H;Myers TA;Jessop L;Delattre O;Yu K;Chanock SJ
由免疫检查点抑制剂和癌基因靶向药物组成的癌症治疗可能会改善癌症治疗，但迄今为止对其综合潜力的研究还很少。为了估计可能受益于这种联合疗法的癌症病例的比例，我们对癌症基因组数据集进行了探索性研究，以确定适合免疫疗法或靶向疗法的体细胞突变谱的比例。我们调查了公共数据库中的 13,349 个基因组图谱，以了解当前药物针对的特定突变或全外显子组非同义突变 (NsM) 负担超过检查点抑制剂反应建议阈值的病例。总体而言，8.9% 的病例表现出可以从联合治疗中受益的特征，这相当于美国每年发生的癌症病例的约 11.2%。常见的靶向突变包括 PIK3CA、BRAF、NF1、NRAS 和 PTEN。我们还注意到，在 SMO、DDR2、FGFR1、PTCH1、FGFR2 和 MET 发生靶向突变的病例中，NsM 负担较高。我们的结果表明，很大一部分实体瘤患者符合免疫靶向联合治疗的条件，他们建议优先考虑特定癌症来试验某些靶向药物和检查点抑制剂药物。
Cancer treatments composed of immune checkpoint inhibitors and oncogene-targeted drugs might improve cancer management, but there has been little investigation of their combined potential as yet. To estimate the fraction of cancer cases that might benefit from such combination therapy, we conducted an exploratory study of cancer genomic data sets to determine the proportion with somatic mutation profiles amenable to either immunotherapy or targeted therapy. We surveyed 13,349 genomic profiles from public databases for cases with specific mutations targeted by current agents or a burden of exome-wide non-synonymous mutations (NsM) that exceeds a proposed threshold for response to checkpoint inhibitors. Overall, 8.9% of cases displayed profiles that could benefit from combination therapy, which corresponded to approximately 11.2% of US annual incident cancer cases. Frequently targetable mutations were in PIK3CA, BRAF, NF1, NRAS and PTEN. We also noted a high burden of NsM in cases with targetable mutations in SMO, DDR2, FGFR1, PTCH1, FGFR2 and MET. Our results indicate that a significant proportion of solid tumor patients are eligible for immuno-targeted combination therapy, and they suggest prioritizing specific cancers for trials of certain targeted and checkpoint inhibitor drugs.