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    EP1.14 - Targeted Therapy (ID 204)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.14-20 - EGFR T790M Mutated Cells Are Not a New Emerging Sub-Clonal Population in Lung Adenocarcinoma After the Treatment of Targeted Therapy (Now Available) (ID 1443)

      08:00 - 18:00  |  Author(s): Li Zhang

      • Abstract
      • Slides

      Background

      EGFR TKI targeted therapy has improved prognosis for lung adenocarcinoma patients. Almost all patients inevitably develop acquired resistance to these agents, mainly through EGFR T790M mutation. Lung adenocarcinoma patients retained the sensitive mutation and simultaneously acquired the T790M resistance mutation. Whether the acquired T790M mutation is in a newly formed cell groups, or they co-exist with the sensitive mutation in the same cell remained unknown.

      Method

      RNA in situ hybridization (ISH) methods were employed to examine EGFR T790M and L858R mutations. EGFR L858R mtation probe was labelled with blue color and T790M was labelled with red color. EGFR mutations were also assessed using PCR methods.

      Result

      Results of RNA ISH and PCR analyses were identical in the majority of examined tissues. We observed that the T790M and L858R mutations co-expressed in the same cell in both the primary and acquired resistance tissue samples. For the two cases with tissues available following third generation TKI therapy, we observed that the T790M mutation disappeared in the repeated biopsy specimen.

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      Conclusion

      The EGFR sensitive mutation is a trunk and drive mutation, while T790M is a gatekeeper mutation that can appear or disappear under the pressure of TKI therapy. EGFR T790M mutation isn't a new emerging cell clone and co-existed with the sensitive mutation in the same cell.

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