ALK阳性非小细胞肺癌患者克唑替尼耐药的机制和治疗措施

Lung cancer is the common lethal disease with the highest morbidity and mortality worldwide. Non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer. Recently, the advances in the molecular biology have transformed our view of NSCLC from histopathological descriptions to precise molecular and genetic identities that can be resolved to single-cell level. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the most crucial tumor driver genes in NSCLC. Their tyrosine kinase inhibitors (TKIs) can significantly improve survival of these patients, who have these driver genes' mutation. Unfortunately, drug resistance would inevitably occur after almost all of initial targeted therapy. The resistance mechanism and corresponding methods on EGFR-TKIs have been reviewed elsewhere and will not be discussed. We will focus on the mechanism of first generation ALK TKI (crizotinib) resistance in patients with ALK positive NSCLC. Likewise, we will also discuss the current therapies for ALK positive NSCLC patients after crizotinib resistance.