Abstract
The ALK gene plays a key role in the pathogenesis of non-small-cell lung cancer (NSCLC). Patients with NSCLC harboring an ALK-rearrangement represent the second oncogene addiction to be identified in this disease. Crizotinib was the first ALK inhibitor showing pronounced clinical activity, and is now a reference treatment for ALK-positive NSCLC disease. However, despite initial impressive responses to crizotinib, acquired resistance almost invariably develops within 12 months. The pressing need for effective second-line agents has prompted the rapid development of next-generation ALK inhibitors. These agents, notably ceritinib and alectinib as the most developed, have a higher potency against ALK than crizotinib, along with activity against tumors harboring crizotinib-resistant mutations and potentially improved CNS penetration.
Original language | English |
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Pages (from-to) | 945-961 |
Number of pages | 17 |
Journal | Future Oncology |
Volume | 12 |
Issue number | 7 |
DOIs | |
Publication status | Published - 1 Apr 2016 |
Keywords
- ALK-rearrangement
- CNS disease
- alectinib
- ceritinib
- crizotinib
- crizotinib-resistance
- non-small-cell lung cancer