Breaking Barriers in Non-small Cell Lung Cancer Treatment: Ceritinib Role in Advancing Targeted Therapy

Abstract

Lung cancer remains the leading cause of cancer-related death globally, with non-small cell lung cancer (NSCLC) accounting for most cases. A critical subset of NSCLC is characterized by anaplastic lymphoma kinase (ALK) gene rearrangements, which drive tumor growth and progression. Targeting this genetic alteration, Ceritinib, a second-generation ALK inhibitor, has shown significant efficacy in both treatment-naive patients and those who have progressed on prior ALK inhibitor therapy. Ceritinib disrupts downstream signaling pathways essential for cancer cell proliferation and survival by inhibiting the ALK fusion protein. Clinical trials such as ASCEND-4 and ASCEND-5 have demonstrated Ceritinib’s superiority over standard chemotherapy, offering improved progression-free G1202R and objective response rates. Despite its benefits, patients often develop resistance to Ceritinib, necessitating ongoing research into combination therapies and next-generation ALK inhibitors. Promising strategies include combining Ceritinib with MEK inhibitors, PD-1/PD-L1 inhibitors, and anti-angiogenic agents to overcome resistance and enhance therapeutic efficacy. Personalized medicine approaches, guided by molecular profiling, are also crucial in optimizing treatment regimens. Moreover, Ceritinib’s potential extends beyond NSCLC, showing promise in treating other ALK-altered malignancies, thereby broadening its clinical applicability. This review comprehensively examines the mechanism of action, clinical efficacy, safety profile, and future perspectives of Ceritinib in managing ALK-positive NSCLC. By highlighting Ceritinib’s pivotal role, we underscore its importance in advancing therapeutic strategies and improving patient care.