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
27P - The prognostic value of neutrophil to lymphocyte ratio (NLR) and 18F-FDG PET SUV in breast cancer patients underwent neoadjuvant chemotherapy
Presenter: Soong June Bae
Session: Poster display session
Resources:
Abstract
28P - Accuracy of core biopsy in predicting pathologic complete response in the breast in patients with complete/near complete clinical and radiological response (Complete Responders in the Breast – CRBr): A feasibility study
Presenter: Nisha Hariharan
Session: Poster display session
Resources:
Abstract
29P - Tumour response to neoadjuvant chemotherapy in breast cancer: Routine pathologic markers improve the predictive power of a cell-loss metric based on release of thymidine kinase 1 into blood
Presenter: Bernhard Tribukait
Session: Poster display session
Resources:
Abstract
30P - Comparison of metabolic changes between neoadjuvant chemotherapy and neoadjuvant endocrine therapy in premenopausal women with ER positive, HER2 negative breast cancer
Presenter: Ho-hyun Ryu
Session: Poster display session
Resources:
Abstract
31P - Circulating miR-155 as a potential therapeutic monitoring marker in breast cancer
Presenter: Sumadi Lukman Anwar
Session: Poster display session
Resources:
Abstract
32P - Profile of breast cancer epidemiology in Sanglah General Hospital, Denpasar, Bali from 2012 to 2019
Presenter: Citra Aryanti
Session: Poster display session
Resources:
Abstract
33P - Contrast enhanced chest CT in patients with breast cancer: Comprehensive imaging analysis and correlation with biological markers
Presenter: Bo Hwa Choi
Session: Poster display session
Resources:
Abstract
34P - Verification of metabolic regulatory mechanisms in androgen receptor-positive triple negative breast cancer
Presenter: Yuka Asano
Session: Poster display session
Resources:
Abstract
35TiP - Ribociclib plus goserelin with hormonal therapy versus physician choice chemotherapy in pre-/perimenopausal patients with HR+, HER2– inoperable locally advanced breast cancer (ABC): RIGHT choice study
Presenter: Yen-Shen Lu
Session: Poster display session
Resources:
Abstract
36TiP - A prospective study to assess response to neoadjuvant hormonal therapy in postmenopausal women with hormone-receptor positive breast cancer at a regional cancer centre in South India
Presenter: Shina Goyal
Session: Poster display session
Resources:
Abstract