Jump to. Interestingly, none of the animals treated with the drug combination showed a regrowth of tumors after treatment interruption Fig. Discussion Although preclinical and clinical researches have explored the interaction of first-generation EGFR-TKIs and cytotoxic agents [ 10 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ], to date there are no data on preclinical combination of chemotherapy with third-generation EGFR-TKIs, such as osimertinib. Additional file 2: Table S1.
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Third generation EGFR inhibitor osimertinib combined with pemetrexed or cisplatin exerts long-lasting anti-tumor effect in EGFR-mutated pre-clinical models of NSCLC
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Analysis of cell proliferation, cell viability and cell death Cell number, cell viability and cell death were evaluated as previously described [ 12 ]. Representative blot of two independent experiments is shown. Nat Genet. Optimization of dosing for EGFR-mutant non-small cell lung cancer with evolutionary cancer modeling. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. Frances Nardinirental mn of sbc a4d4 pismo and tc cues
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As illustrated in Fig. However, the acquisition of EGFR TM secondary mutation, the substitution of threonine with methionine, is responsible for half of the cases of acquired resistance to TKI treatment [ 1 ]. Finally, we demonstrated that osimertinib resistant clones, either derived from resistant tumors or generated in vitro, were less sensitive to pemetrexed prompting to use a chemotherapy regimen non-containing pemetrexed in patients after progression to osimertinib treatment.
By contrast, the combination of osimertinib with pemetrexed or cisplatin prevented or at least delayed the acquisition of resistance and inhibited regrowth when treatment was stopped with tumor cure. Jump to. Subsequently, four of eight animals treated with osimertinib alone developed acquired resistance. Next article same sex marriage definition