[Molecular mechanisms of targeted drug resistance in lung cancer and its therapeutic strategy].
Several driver oncogenes, including EGFR mutations and ALK rearrangement, have been identified in lung cancer. The EGFR tyrosine kinase inhibitors (TKIs) and ALK-TKIs show dramatic effects against lung cancer with EGFR activating mutations and ALK rearrangements, respectively. However, 20% of EGFR mutant lung cancer patients show intrinsic resistance, and the responders almost invariably acquire resistance to EGFR-TKIs within several years. Several mechanisms, including secondary mutations in EGFR or ALK, activation of alternative pathway, have been reported to contribute to resistance to EGFR-TKIs and ALK-TKIs. New generation TKIs for overcoming resistance to EGFR-TKI or ALK-TKI are being evaluated in clinical trials. Further investigations to develop optimal therapy based on accurate diagnosis of resistant mechanism are warranted to improve the success of treatment with targeted drugs in lung cancer.
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D000077548:Anaplastic Lymphoma Kinase; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D058990:Molecular Targeted Therapy; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics
D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases