Lung cancer in the era of precision medicine.
Lung cancer in the era of precision medicine.
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DOI：
10.1158/1078-0432.ccr-14-2748
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发表时间：
2015-05-15
期刊：
影响因子：
--
通讯作者：
Herbst RS
中科院分区：
文献类型：
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作者：
Politi K;Herbst RS
过去的十年对肺癌患者、医生和科学家来说都是变革性的。2004年，在肺腺癌中发现了EGFR突变，这种突变赋予了对酪氨酸激酶抑制剂的敏感性，这预示着肺癌精准医学时代的开始。它还促使许多研究人员共同努力，以定义肺癌的分子亚组，表征肺癌亚型的基因组景观，确定新的治疗靶点，并定义对靶向治疗的敏感性和耐药性机制。这些努力的成果现在每天都在肺癌诊所可见：患者接受分子检测以确定他们的肿瘤是否含有可操作的突变，可以克服对第一代药物耐药性的新的和改进的靶向治疗正在临床试验中，靶向免疫系统的药物在患者中显示出活性。这一非凡的承诺被一个令人清醒的事实所冲淡，即即使是最新的转移性疾病治疗方法也很少有疗效，而且只对一小部分患者有效。持续和未来的努力，以发现肺癌的新弱点，解开耐药性的复杂性，提高免疫疗法的疗效和进行生物标志物驱动的临床试验是必要的，以改善肺癌患者的结果。
The past decade has been transformative for lung cancer patients, physicians and scientists. The discovery of EGFR mutations that confer sensitivity to tyrosine kinase inhibitors in lung adenocarcinomas in 2004 heralded the beginning of the era of precision medicine for lung cancer. It also precipitated concerted efforts by many investigators to define molecular subgroups of lung cancer, characterize the genomic landscape of lung cancer subtypes, identify novel therapeutic targets and define mechanisms of sensitivity and resistance to targeted therapies. The fruits of these efforts are visible every day now in lung cancer clinics: patients receive molecular testing to determine whether their tumor harbors an actionable mutation, new and improved targeted therapies that can overcome resistance to first-generation drugs are in clinical trials and drugs targeting the immune system are showing activity in patients. This extraordinary promise is tempered by the sobering fact that even the newest treatments for metastatic disease are rarely curative and are effective only in a small fraction of patients. Ongoing and future efforts to find new vulnerabilities of lung cancers, unravel the complexity of drug resistance, increase the efficacy of immunotherapies and perform biomarker-driven clinical trials are necessary to improve outcomes for lung cancer patients.