Colli Leandro M, Machiela Mitchell J, Zhang Han, Myers Timothy A, Jessop Lea, Delattre Olivier, Yu Kai, Chanock Stephen J
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
Cancer Res. 2017 Jul 1;77(13):3666-3671. doi: 10.1158/0008-5472.CAN-16-3338. Epub 2017 Apr 26.
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 datasets 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 nonsynonymous mutations (NsM) that exceed 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 U.S. annual incident cancer cases. Frequently targetable mutations were in , and We also noted a high burden of NsM in cases with targetable mutations in , and 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. .
由免疫检查点抑制剂和癌基因靶向药物组成的癌症治疗方案可能会改善癌症治疗效果,但目前对其联合应用潜力的研究还很少。为了评估可能从这种联合治疗中获益的癌症病例比例,我们对癌症基因组数据集进行了一项探索性研究,以确定具有适合免疫治疗或靶向治疗的体细胞突变谱的病例比例。我们从公共数据库中调查了13349个基因组图谱,寻找那些具有当前药物所靶向的特定突变,或外显子组范围内非同义突变(NsM)负担超过对检查点抑制剂反应的建议阈值的病例。总体而言,8.9%的病例显示出可从联合治疗中获益的图谱,这相当于美国每年新发癌症病例的约11.2%。常见的可靶向突变位于 ,并且 我们还注意到在 、 和 中具有可靶向突变的病例中NsM负担较高。我们的结果表明,相当一部分实体瘤患者适合免疫靶向联合治疗,并且建议针对某些靶向和检查点抑制剂药物的试验优先考虑特定癌症。