A Novel Molecular Target in Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer treated with a Combination of Osimertinib and Pemetrexed

In this study, we evaluate the therapeutic potential of combining osimertinib with pemetrexed and clarify the underlying molecular mechanisms in order to establish novel therapeutic strategies for EGFR-mutant NSCLC. We found that the combination of osimertinib and pemetrexed could induce strong apoptotic activity and enhance anti-tumor effects compared to monotherapy in two NSCLC cell lines harboring an EGFR mutation. In addition, we have identified PLK1 as a therapeutic target for combination therapy and as a promising treatment target for overcoming resistance to osimertinib in EGFR-mutated NSCLC patients. Antiproliferative effects of osimertinib+pemetrexed were assessed using PC-9 and H1975 cells harboring EGFR mutations by the MTT assay. GeneChip Human Gene 2.0 Sense Target arrays were used to assess gene expression on exposure to osimertinib in the presence or absence of pemetrexed. Cell lines resistant to osimertinib as well as those resistant to the combination of osimertinib and pemetrexed were established in order to explore mechanisms of resistance.