Center of Integrated Oncology Köln-Bonn, University of Cologne, Weyertal 115b, 50931 Cologne, Germany.
J Clin Oncol. 2013 May 20;31(15):1858-65. doi: 10.1200/JCO.2012.45.9867. Epub 2013 Apr 15.
The advent of novel therapeutics that specifically target signaling pathways activated by genetic alterations has revolutionized the way patients with lung cancer are treated. Although only few and largely ineffective chemotherapeutic regimens were available 10 years ago, a lung tumor diagnosed today requires extensive pathologic subtyping and diagnosis of genome alterations to afford more effective treatment (eg, in EGFR-mutant adenocarcinoma). This change of paradigm has several profound implications, ranging from preclinical work on the mechanism of action to a novel, more biologically oriented taxonomy and from genome diagnostics to trial design. Here, we have summarized these developments into six conceptual paradigms that illustrate the transition from empirical cancer medicine to mechanistically based individualized oncology.
新型治疗药物的出现,专门针对遗传改变激活的信号通路,彻底改变了肺癌患者的治疗方式。尽管 10 年前仅有少数且在很大程度上无效的化疗方案可用,但如今诊断出的肺部肿瘤需要进行广泛的病理亚型分析和基因组改变诊断,以提供更有效的治疗方法(例如,针对 EGFR 突变型腺癌)。这种范式的转变具有深远的影响,从作用机制的临床前研究到新的、更具生物学导向的分类学,以及从基因组诊断到临床试验设计。在这里,我们将这些发展总结为六个概念范式,说明了从经验性癌症医学向基于机制的个体化肿瘤学的转变。