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Lung cancer has already been one of the major reasons of cancer-related deaths, with anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC)taking up about 5%. This type of tumor has a high rate of central nervous system metastasis and standard chemotherapy has limited effect to effectively control progression. ALK-targeted inhibitors (ALK-TKIs) have notably extended the lifespan of patients with ALK-positive NSCLC, and third-generation inhibitors, in particular, have made significant progress in overcoming drug resistance and increasing intracranial activity, with particular efficacy in patients with brain metastases. However, these improvements still do not fully meet clinical needs, and drug resistance and adverse effects remain major challenges. This article reviews the molecular mechanisms of ALK rearrangements, the efficacy and resistance mechanisms of various generations of inhibitors, and discusses future therapeutic strategies and challenges.
Wenjie Ni (Fri,) studied this question.