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Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.

miR-200c in extracellular vesicles as a circulating biomarker of EGFR-TKI response and a mediator of EGFR-TKI sensitivity in heterogeneous NSCLC.

Sub-category:
Metastatic Non-Small Cell Lung Cancer

Category:
Lung Cancer—Non-Small Cell Metastatic

Meeting:
2019 ASCO Annual Meeting

Abstract No:
e20547

Citation:
J Clin Oncol 37, 2019 (suppl; abstr e20547)

Author(s): Chienchung Lin, Wu-Chou Su; Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan, Tainan City, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

Abstract Disclosures

Abstract:

Background: Through intercellular transfer of EV(extracellular vesicles) miRNA, tumor cells can confer drug resistance to each other and contribute to tumor heterogeneity. However, the mechanisms why EGFR-TKI can be effective in heterogeneous NSCLC with low abundances of EGFR mutations remain unknown. The aim of the study is to investigate the significance of EV miRNA in mediating the efficacy of EGFR-TKI in heterogeneous NSCLC and serving as the biomarker of response to EGFR-TKI. Methods: We first evaluate if EVs from EGFR mutant cell (PC9) can affect EGFR-TKI sensitivity of EGFR wild type cell (CL1-5, H1299) in vitro co-culture system and in vivo. We then identified the differential miRNA panel by comparing EVs from PC9 to those from CL1-5. Finally, we verified if the expressions level of these miRNA are different in blood EVs from patient with good response compared to those with poor response to EGFR-TKI. Results: We first verified that CL1-5 can take up labelled EVs from PC9 under time-lapse microscope and EGFR mutant DNA can be detected in recipient EGFR wild-type cell using digital PCR. We found EVs from PC9 enhanced gefitinib sensitivity of CL1-5. And co-culturing PC9 with CL1-5 enhanced CL1-5 gefitinib sensitivity which was reversed by adding GW4789, the inhibitor of exosome secretion. In subcutaneous CL1-5 animal model, in comparison to treating with gefitinib or PC9 EVs alone, only the combination treatment with gefitinib and PC9 EVs delayed cancer growth. Using small RNA sequencing, we identified a unique miRNA profile allowing discriminating EV from PC9 cells to those from CL1-5; MiRNA 200 family including 200a, 200b, 200c and mir429 were up-regulated significantly in PC9 EV. From Aug 2015 to Sep 2017, sixteen patients with good response (PFS > 12M) or poor response (PFS < 6M) to EGFR-TKI were enrolled and blood were collected for EV miRNA isolation. Ten of these blood samples were qualified for miRNA analysis and mir200a and 200c were found up-regulated in good responder to EGFR-TKI. The transfection of mir200c in CL1-5 cells not only inhibited the oncogenic pathway contributing to EGFR-TKI resistance including Stat3, Akt, EMT and BIM pathway but also enhanced gefitinib sensitivity of CL1-5 cells. Conclusions: Our data suggested mir200c from blood EV serve as a biomarker of response to EGFR-TKI and mir200c may mediate EGFR-TKI sensitivity in heterogenous EGFR mutant NSCLC.

 
Other Abstracts in this Sub-Category:

 

1. Association of STK11/LKB1 genomic alterations with lack of benefit from the addition of pembrolizumab to platinum doublet chemotherapy in non-squamous non-small cell lung cancer.

Meeting: 2019 ASCO Annual Meeting Abstract No: 102 First Author: Ferdinandos Skoulidis
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

2. Real-world outcomes of patients with advanced non-small cell lung cancer (aNSCLC) and autoimmune disease (AD) receiving immune checkpoint inhibitors (ICIs).

Meeting: 2019 ASCO Annual Meeting Abstract No: 110 First Author: Sean Khozin
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

3. RELAY: A multinational, double-blind, randomized Phase 3 study of erlotinib (ERL) in combination with ramucirumab (RAM) or placebo (PL) in previously untreated patients with epidermal growth factor receptor mutation-positive (EGFRm) metastatic non-small cell lung cancer (NSCLC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 9000 First Author: Kazuhiko Nakagawa
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

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