International Journal of Hematology and Oncology
2025, Vol 35, Num 1 Page(s): 60-68
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Treatment After Crizotinib Resistance in ALK+ Non-Small-Cell Lung Cancer
Seher N. KAZAZ1, Ilhan OZTOP2
1Kanuni Research and Training Hospital, Medical Oncology, Trabzon, TURKEY
2Dokuz Eylül University, Institute of Oncology, Department of Medical Oncology, Izmir, TURKEY
Keywords: Non-small-cell lung cancer, ALK, Crizotinib, Resistance
Systemic chemotherapy, genotype-based targeted therapies and immunotherapy are widely used in the treatment of advanced nonsmall- cell lung cancer (NSCLC). Among the targeted therapies, the agents targeting the epidermal growth factor receptor (EGFR), the echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement and C-ros oncogene 1 (ROS-1) have currently become standard treatment for cases presenting such molecular anomalies. Of them, cases with ALKrearrangement displayed dramatic results with a first generation ALK-inhibitor crizotinib; however, most of the patients develop a resistance in a few years. Especially the central nervous system relapses pose the most common clinical problem. Next generation ALK-inhibitors are promising with a high level of effectiveness in this resistance, in which various molecular mechanisms take part. Also, it gains increasing importance to re-perform a biopsy in the progression stage and reveal the mechanisms causing the secondary resistance in those patients.
Seher N. KAZAZ1, Ilhan OZTOP2
1Kanuni Research and Training Hospital, Medical Oncology, Trabzon, TURKEY
2Dokuz Eylül University, Institute of Oncology, Department of Medical Oncology, Izmir, TURKEY
Keywords: Non-small-cell lung cancer, ALK, Crizotinib, Resistance
Systemic chemotherapy, genotype-based targeted therapies and immunotherapy are widely used in the treatment of advanced nonsmall- cell lung cancer (NSCLC). Among the targeted therapies, the agents targeting the epidermal growth factor receptor (EGFR), the echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement and C-ros oncogene 1 (ROS-1) have currently become standard treatment for cases presenting such molecular anomalies. Of them, cases with ALKrearrangement displayed dramatic results with a first generation ALK-inhibitor crizotinib; however, most of the patients develop a resistance in a few years. Especially the central nervous system relapses pose the most common clinical problem. Next generation ALK-inhibitors are promising with a high level of effectiveness in this resistance, in which various molecular mechanisms take part. Also, it gains increasing importance to re-perform a biopsy in the progression stage and reveal the mechanisms causing the secondary resistance in those patients.
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