Expanding individualized therapeutic options via genoproteomics
Expanding individualized therapeutic options via genoproteomics
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DOI：
10.1016/j.canlet.2023.216123
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发表时间：
2023-03-28
期刊：
影响因子：
9.7
通讯作者：
Qin，Jun
中科院分区：
文献类型：
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作者：
Zhan，Dongdong;Zheng，Nairen;Qin，Jun
临床下一代测序（NGS）2测试为驱动基因突变的癌症患者提供了治疗建议。目前尚无针对无驱动基因突变患者的靶向治疗方案。在此，我们对169例福尔马林固定石蜡包埋（FFPE）3例非小细胞肺癌（NSCLC， 65例）、4例结直肠癌（CRC， 61例）、5例甲状腺癌（THCA， 14例）、6例胃癌（GC， 2例）、7例胃肠道间质瘤（GIST， 11例）、8例恶性黑色素瘤（MM， 6例）进行了NGS和蛋白质组学检测。在169例样本中，NGS在73例样本中检测到14个可操作的突变基因，为43%的患者提供了治疗方案。蛋白质组学确定了61个可操作的临床药物靶点，这些靶点已被FDA批准或正在122个样本中进行临床试验，为72%的患者提供了治疗选择。体内实验表明，丝裂原活化蛋白激酶（MEK）10抑制剂诱导MEK1 （Map2k1）过表达，阻断小鼠肺肿瘤生长。因此，蛋白质过表达是指导靶向治疗的潜在可行指标。总的来说，我们的分析表明，结合NGS和蛋白质组学（基因蛋白质组学）可以将靶向治疗选择扩大到85%的癌症患者。
Clinical next-generation sequencing (NGS)2tests have enabled treatment recommendations for cancer patients with driver gene mutations. Targeted therapy options for patients without driver gene mutations are currently unavailable. Herein, we performed NGS and proteomics tests on 169 formalin-fixed paraffin-embedded (FFPE)3samples of non-small cell lung cancers (NSCLC, 65),4colorectal cancers (CRC, 61),5thyroid carcinomas (THCA, 14),6gastric cancers (GC, 2),7gastrointestinal stromal tumors (GIST, 11),8and malignant melanomas (MM, 6).9Of the 169 samples, NGS detected 14 actionable mutated genes in 73 samples, providing treatment options for 43% of the patients. Proteomics identified 61 actionable clinical drug targets approved by the FDA or undergoing clinical trials in 122 samples, providing treatment options for 72% of the patients.In vivoexperiments demonstrated that the Mitogen-Activated Protein Kinase (MEK)10inhibitor induced the overexpression of MEK1 (Map2k1) to block lung tumor growth in mice. Therefore, protein overexpression is a potentially feasible indicator for guiding targeted therapies. Collectively, our analysis suggests that combining NGS and proteomics (genoproteomics) could expand the targeted treatment options to 85% of cancer patients.