Ceritinib—a second-generation ALK inhibitor overcoming resistance in ALK-rearranged non-small cell lung cancer
For many years, standard first-line systemic therapy for metastatic non-small cell lung cancer (NSCLC) has consisted of platinum-based combination chemotherapy. The description of activating mutations in the epidermal growth factor receptor (EGFR) and the investigation of specific tyrosine kinase inhibitors (TKIs) inhibiting the EGFR signaling pathway changed this treatment paradigm. In the last few years, many genetic aberrations (mutations, translocations) have been described in NSCLC and some of them can be targeted by specific inhibitors. These genetic aberrations are believed to be the driver of lung cancer carcinogenesis and progression. Targeted therapies significantly increase overall response rates (ORR), diseasefree survival (DFS) and overall survival (OS) compared to conventional chemotherapy. EGFR mutations are found in 10-15% of adenocarcinoma patients in Western countries. Chromosomal rearrangements of anaplastic lymphoma kinase (ALK) are detected in 1.6% to 8.6% of unselected NSCLC patients (1). ALK translocations are found nearly exclusively in lung adenocarcinomas, as opposed to other histopathological subtypes.