Targeted therapies in advanced non-small-cell lung cancer: new biomarkers and treatment strategies.

Biomarker-matched therapies now improve outcomes in an increasing number of molecularly defined subgroups.

现在，生物标志物匹配的疗法在越来越多的分子定义的亚组中改善了结果。

In this second paper in a Series on therapeutics in lung cancer, we summarise recent advances in NSCLC with established alterations, including EGFR, ALK, ROS1, KRAS, BRAF, RET, HER2, MET, and NTRK, and discuss emerging targets, such as NRG1 fusions, MTAP loss, and SMARCA4 deficiency.

在这篇关于肺癌治疗系列的第二篇文章中，我们总结了具有已知改变的NSCLC的最新进展，包括EGFR、ALK、ROS1、KRAS、BRAF、RET、HER2、MET和NTRK，并讨论了新兴的靶点，如NRG1融合、MTAP缺失和SMARCA4缺陷。

Newer generations of tyrosine kinase inhibitors, the introduction of bispecific antibodies, and antibody-drug conjugates have improved response durability, intracranial disease control, and in some settings, overall survival. However, durable benefit can remain limited by acquired resistance, tumour heterogeneity, lineage plasticity, and off-target escape, supporting repeat tissue biopsy and circulating-tumour DNA profiling to guide subsequent treatment.

新一代酪氨酸激酶抑制剂、双特异性抗体的引入以及抗体药物偶联物已经改善了反应的持久性、颅内疾病的控制，以及在某些情况下，总体生存率。然而，由于获得性耐药、肿瘤异质性、谱系可塑性和靶外逃逸，持久的益处可能仍然有限，支持重复组织活检和循环肿瘤DNA分析以指导后续治疗。

With several options available such as monotherapy and combination approaches, individualised treatment selection is becoming increasingly complex.

随着单药治疗和联合治疗等多种选择的出现，个体化治疗选择变得越来越复杂。

We discuss these choices, including the management of CNS disease and oligoprogression, and long-term tolerability.

我们讨论了这些选择，包括中枢神经系统疾病的管理、寡进展的管理以及长期耐受性。

As drug development extends beyond canonical drivers to rarer alterations and adverse co-mutations, the range of targetable disease is increasing.

随着药物开发从典型驱动因素扩展到更罕见的改变和不良共突变，可靶向疾病的范围正在增加。

Further progress will depend on more effective and adaptive treatment strategies together with equitable access to comprehensive molecular profiling, timely biomarker testing, and next-generation targeted therapies.

进一步的进展将取决于更有效和适应性强的治疗策略，以及对全面分子分析、及时的生物标志物测试和新一代靶向疗法的公平获取。