Department of Health Sciences, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy.
Transl Lung Cancer Res. 2015 Feb;4(1):5-7. doi: 10.3978/j.issn.2218-6751.2014.07.02.
The anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase involved in the onset of several malignancies. In particular, ALK is the driving oncogenic lesion in a small but significant fraction of non-small cell lung cancer (NSCLC) patients. ALK+ NSCLCs can be treated with the dual ALK/MET inhibitor crizotinib, with better outcome compared to standard chemotherapy. However, relapses frequently occur, due to various mechanisms, limiting overall efficacy of the treatment. Point mutations within the ALK catalytic domain or ALK gene amplification account for approximately 30-40% of crizotinib-resistant cases, suggesting that the diseases still relies on ALK activity and that more potent inhibitors could be useful in this setting. Ceritinib is a novel selective ALK inhibitor with preclinical activity against crizotinib-resistant ALK mutants. A recent article in the New England Journal of Medicine reports on clinical evaluation of ceritinib. Response rate and progression-free survival (PFS) were comparable to crizotinib, but most importantly, crizotinib-resistant patients were successfully treated, with efficacy similar to crizotinib-naïve patients. The study extends the array of available anti-ALK drugs. Based on these data, ceritinib was approved by FDA in April 2014.
间变性淋巴瘤激酶（ALK）是一种受体酪氨酸激酶，参与多种恶性肿瘤的发生。特别是，ALK 是一小部分非小细胞肺癌（NSCLC）患者中致癌驱动基因病变。ALK+NSCLC 可采用双重 ALK/MET 抑制剂克唑替尼治疗，与标准化疗相比，具有更好的疗效。然而，由于多种机制，经常会发生复发，限制了治疗的总体效果。ALK 催化结构域内的点突变或 ALK 基因扩增约占克唑替尼耐药病例的 30-40%，这表明疾病仍然依赖于 ALK 活性，并且在这种情况下，更有效的抑制剂可能会有用。塞瑞替尼是一种新型选择性 ALK 抑制剂，对克唑替尼耐药的 ALK 突变体具有临床前活性。《新英格兰医学杂志》上的一篇最新文章报道了塞瑞替尼的临床评估。反应率和无进展生存期（PFS）与克唑替尼相当，但最重要的是，成功地治疗了克唑替尼耐药的患者，疗效与克唑替尼初治患者相似。该研究扩展了可用的抗 ALK 药物范围。基于这些数据，塞瑞替尼于 2014 年 4 月获得美国食品和药物管理局（FDA）的批准。
