Thus, EV (let-7b-5p, miR-184) and circulating (miR-22-3p) plasma miRNA likely modulate NSCLC response to Osimertinib, highlighting a novel mechanism of resistance and suggesting that these biomarkers may assist in the selection of patients that will likely benefit from Osimertinib/AKT blockade combination treatments. Here, AKT1 is linked to non-small cell lung carcinoma.