Abstract 389P
Background
Patient-derived cancer organoid (PDOs) models have proven with powerful research value and significant clinical application prospects. However, we still know little about organoid models of non-small cell lung cancer (NSCLC). This study aims to characterize the consistency of genomic variations between the primary tumours and PDOs, and to explore utility of PDOs as preclinical models to predict the treatment response for the precision medicine.
Methods
Tumour samples were collected for organoid culture. Primary tumour and PDO samples were analysed by whole exon sequencing (WES). C-MET overexpression of tissue was test by immunohistochemistry. Antineoplastic drugs were tested by the PDOs. Cell viability was measured by Cell Titer Glo assay 7-10 days after drug treatment. Heatmap of log IC50 values were calculated from drug response analyses of PDOs by applying nonlinear regression (curve fit).
Results
A total of 7 patients (pts) (I-III stage) were enrolled. 7 paired surgical tumour and PDOs were analysed, respectively. Comparison of gene mutations of top 20 ranked genes related with lung cancer, the concordance were over 80% between tumour and PDOs in 5 pts. The concordances of the other 2 pts were less than 50%. Both tissues and PDOs harbored driver mutations in 4 pts (2 EGFR L858R, 1 EGFR EX20 ins and 1 KRAS G12C ). Drug screen was carried out by using 26 antineoplastic drugs in the 7 PDOs in vitro. Of the 2 PDOs with EGFR L858R, one displayed the most significant response to Gefitinib, the other showed resistance to Gefitinib but significant response to Osimertinib, whose matched tissue showed c-MET overexpression indicating a mechanism of resistant to Gefitinib. The PDO with EGFR EX20 ins also indicated resistance to Gefitinib but significant response to Osimertinib in accordance with public articles.
Conclusions
Patient-derived lung cancer organoids could provide us a practical model system for studying NSCLC and predict treatment response for personal precision medicine.
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
YO20 - Can "Superman" have Chronic Myelomonocytic Leukemia?
Presenter: Alexander Luchinin
Session: Poster display session
Resources:
Abstract
YO21 - Sanctuary Site Central Nervous System Relapse-Refractory DLBCL Responding to Nivolumab and Lenalidomide.
Presenter: Irappa Madabhavi
Session: Poster display session
Resources:
Abstract
YO22 - External Auditory Canal Mass: A Case Series of Squamous Cell Carcinoma
Presenter: Mel Valerie Cruz-Ordinario
Session: Poster display session
Resources:
Abstract
YO23 - Soft tissue Giant cell tumor presented as Nasopharyngeal mass: A case report
Presenter: Emmelyn Buenacosa-Nepucpan
Session: Poster display session
Resources:
Abstract
YO25 - Hyperprogression after pembrolizumab in recurrent oropharyngeal cancer and the use of nab-paclitaxel as salvage treatment- A case report.
Presenter: Izzati Rosli
Session: Poster display session
Resources:
Abstract
YO26 - Exacerbation of radiation necrosis around the radiotherapy-pretreated brain metastases site after immune checkpoint inhibitors.
Presenter: Minako Nishio
Session: Poster display session
Resources:
Abstract
YO27 - Comparative Study Of 20Gray/5Fraction And 30Gray/10 Fraction Whole Brain Radiation In Brain Metastasis
Presenter: Pradip Bhandari
Session: Poster display session
Resources:
Abstract
YO28P - The response to anaplastic lymphoma kinase (ALK) inhibitor in metastatic anaplastic thyroid carcinoma (ATC)
Presenter: Nur Faizah Ab Muin
Session: Poster display session
Resources:
Abstract
YO29 - Acute kidney injury secondary to bilateral renal artery tumor thrombosis in a case of posterior mediastinal undifferentiated sarcoma: case report
Presenter: Ritsu Ibusuki
Session: Poster display session
Resources:
Abstract
YO30 - Follicular dendritic cell sarcoma of the tonsil- a multimodality approach
Presenter: Rich Ericson King
Session: Poster display session
Resources:
Abstract