Abstract 60P
Background
MET exon14 skipping mutations are considered an important driver of oncogenesis and are observed in approximately 3-4% of patients diagnosed with non-small cell lung cancer (NSCLC). Various MET tyrosine kinase inhibitors (TKIs) are currently being developed for clinical use in the treatment of NSCLC patients with MET exon14 skipping mutation. However, preclinical research in this area has been restricted due to the rarity of MET exon14 mutant cases. Almost all the studies conducted have been on patients or patent-derived xenografts (PDX). To address this issue, there is a need for a NSCLC cell line with MET exon14 skipping mutation. In this study, we have established a novel lung adenocarcinoma cell line that harbors MET exon14 skipping mutation. This new cell line represents a valuable tool for the research of MET targeted therapy.
Methods
The cell line was established using the primary tumor tissue from a 67-year-old male patient with NSCLC, and named as HX-JCJ. The cell line has been growing well for more than 10 months and has been passaged over 50 times. Phenotypes of the cell line, such as proliferation, invasion, protein expression, and xenografting were characterized in vitro and in vivo. MET ex14 skipping mutation of this cell line was validated by RT-PCR and Sanger sequencing.
Results
Drug screen showed that this cell line was extremely sensitive to KC1036 (IC50=4.8nm), which is a home-made small molecule inhibitor with strong anti-MET and anti-angiogensis activity.
Conclusions
In conclusion, we successfully established a novel NSCLC cell line (HX-JCJ) harboring MET ex14 skipping mutation from the primary tumor tissue, which may provide a promising cell model for further MET relevant research.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
78P - Peroxiredoxin-1 knockout negatively affects the viability of ph+ B-cell acute lymphoblastic leukemia cells and sensitizes them to tyrosine kinase inhibitors
Presenter: Jaromir Hunia
Session: Poster session 09
79P - Co-delivered crizotinib and gefitinib based on nanoparticle for synergically overcoming resistance lung adenocarcinoma treatment
Presenter: Haiyu Zhou
Session: Poster session 09
80P - Steroidal oximes: A new potential therapeutic approach for cancer treatment
Presenter: Mafalda Laranjo
Session: Poster session 09
81P - miR-23b and -133a role on TRAIL-induced apoptosis pathway components expression and TRAIL sensitization in lung adenocarcinoma cells
Presenter: Denise Leite
Session: Poster session 09
83P - Impact of VHL-associated tumor treatment on mental health: An international patient survey
Presenter: Othon Iliopoulos
Session: Poster session 09
84P - Microenvironment immune differences between sexes in multiple myeloma
Presenter: Maria de los Angeles Clavo
Session: Poster session 09
85P - In silico evaluation of the transcriptomic and immunologic profile of lung adenocarcinomas with deletions or disruptive mutations of SMARCA4
Presenter: Ester Garcia Lorenzo
Session: Poster session 09
86P - Effect of chemotherapy-induced autophagic secretome on natural killer cell activity
Presenter: Ayfer Karlitepe
Session: Poster session 09
87P - WIP1 phosphatase promotes etoposide induced autophagy in medulloblastoma and neuroblastoma
Presenter: Hatice Pilevneli
Session: Poster session 09
88P - PPM1D/WIP1 phosphatase mediates basal and genotoxic stress-induced autophagy via ULK-1 de-phosphorylation
Presenter: Ceylan Ak
Session: Poster session 09