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Osimertinib is the current recommended treatment for EGFR T790M-positive NSCLC following EGFR-TKI therapy. However, resistance to osimertinib therapy is inevitably acquired after a period of effective treatment. We had a patient suffering from EGFR L858R/T790M-positive NSCLC who initially responded to osimertinib therapy but eventually developed resistance. Plasma cell-free DNA analysis revealed the occurrence of exon-16-skipping HER2, which may resulted in the HER2 splice variant, HER2D16. HER2D16 has never been reported in lung cancer, and HER2D16-driven signaling was known to be regulated by Src-kinase in breast cancer. We investigated the role of HER2D16 as an osimertinib-resistant mechanism.
PMID: 31557536 [PubMed - as supplied by publisher]