The findings of this study demonstrate that osimertinib-resistant cells exhibit increased sensitivity to paclitaxel and chloroquine (CQ), indicating that a combination therapy consisting of osimertinib, microtubule-stabilizing agents (e.g., paclitaxel), and autophagy-lysosome inhibitors (e.g., CQ) constitutes a rational therapeutic strategy for clinical trials targeting CAMSAP3-low NSCLC. Here, CAMSAP3 is linked to non-small cell lung carcinoma.