Cortinovis D, Abbate M, Bidoli P, Capici S, Canova S
Medical Oncology Unit, AOU San Gerardo, via Giambattista Pergolesi 33, 20900 Monza, Italy.
Ecancermedicalscience. 2016 Jun 23;10:648. doi: 10.3332/ecancer.2016.648. eCollection 2016.
Non-small-cell lung cancer is still considered a difficult disease to manage because of its aggressiveness and resistance to common therapies. Chemotherapy remains the gold standard in nearly 80% of lung cancers, but clinical outcomes are discouraging, and the impact on median overall survival (OS) barely reaches 12 months. At the end of the last century, the discovery of oncogene-driven tumours completely changed the therapeutic landscape in lung cancers, harbouring specific gene mutations/translocations. Epidermal growth factors receptor (EGFR) common mutations first and anaplastic lymphoma kinase (ALK) translocations later led new insights in lung cancer biology knowledge. The use of specific tyrosine kinases inhibitors overturned the biological behaviour of EGFR mutation positive tumours and became a preclinical model to understand the heterogeneity of lung cancers and the mechanisms of drug resistance. In this review, we summarise the employment of targeted agents against the most representative biomolecular alterations and provide some criticisms of the therapeutic strategies.
非小细胞肺癌因其侵袭性和对常见疗法的耐药性,至今仍被视为一种难以治疗的疾病。化疗仍是近80%肺癌的金标准,但临床疗效令人沮丧,对中位总生存期(OS)的影响 barely reaches 12个月。上世纪末,癌基因驱动肿瘤的发现彻底改变了携带特定基因突变/易位的肺癌治疗格局。表皮生长因子受体(EGFR)常见突变首先出现,随后间变性淋巴瘤激酶(ALK)易位,为肺癌生物学知识带来了新见解。特异性酪氨酸激酶抑制剂的使用颠覆了EGFR突变阳性肿瘤的生物学行为,并成为理解肺癌异质性和耐药机制的临床前模型。在本综述中,我们总结了针对最具代表性生物分子改变的靶向药物的应用,并对治疗策略提出了一些批评。