Personalized treatment options for ALK-positive metastatic non-small-cell lung cancer: potential role for Ceritinib.

摘要: The fusion of echinoderm microtubule-associated protein-like 4 with the anaplastic lymphoma kinase (EML4-ALK) is found in 3%-7% non-small-cell lung cancer (NSCLC) cases and confers sensitivity to crizotinib, first United States Food Drug Administration (FDA)-approved ALK inhibitor drug. Although crizotinib has an excellent initial therapeutic effect, acquired resistance this drug invariably develops within year treatment. Resistance may involve secondary gatekeeper mutations gene interfering crizotinib-ALK interactions, or compensatory activation aberrant bypass signaling pathways. New strategies overcome are needed. Ceritinib, a second-generation inhibitor, overcomes several crizotinib-resistant demonstrated efficacy against tumor growth vitro vivo preclinical models resistance. Notably, dose-escalation Phase I ASCEND-1 trial shown marked activity ceritinib both crizotinib-naive ALK-rearranged cancer. overall response rate was 58% subgroup patients late-stage NSCLC. discontinuation due toxicity 10%. standard dose established at 750 mg daily. This paper outlines pathogenesis treatment ALK-positive cancer, focuses on clinical results surrounding accelerated FDA approval for metastatic NSCLC who have progressed on/or intolerant, discusses potential efforts seeking maximize expand its usage other indications therapy.