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
15P - Comparing the outcomes of the mastectomy using the tumescent technique by between the special and non-special surgeons
Presenter: Naoya Takeda
Session: Poster display session
Resources:
Abstract
16P - Risk factors and prognostic value of non-alcoholic fatty liver disease (NAFLD) in hormone positive, non-metastatic breast cancer receiving adjuvant hormonal therapy
Presenter: Kartika Taroeno Hariadi
Session: Poster display session
Resources:
Abstract
17P - Distance related outcome in indigenous and non-indigenous breast cancer women of Western Australia
Presenter: Azim Khan
Session: Poster display session
Resources:
Abstract
18P - Usefulness of neutrophil to lymphocyte ratio in early stage breast cancer as predictor of disease-free survival in a Babylon Oncology Center
Presenter: Yaala Raof Al-Bairmany
Session: Poster display session
Resources:
Abstract
19P - Silymarin functionalized quantum cores as selective inhibitor of polo-like kinase 1, and preclinical antitumor activity in human breast cancer xenografts
Presenter: Manickam Paulpandi
Session: Poster display session
Resources:
Abstract
20P - Diagnostic value of serum HER-2 level in compression with tissue HER-2 in breast cancer: A systematic review and meta-analysis
Presenter: Amir Shamshirian
Session: Poster display session
Resources:
Abstract
21P - Clinical outcome of treatment without trastuzumab in HER2 positive breast cancer patients
Presenter: Than Than Aye
Session: Poster display session
Resources:
Abstract
22P - Clinical outcomes after skin-sparing or nipple areolar complex-sparing mastectomy with sentinel lymph node biopsy in early breast cancer patients
Presenter: Hye Yoon Lee
Session: Poster display session
Resources:
Abstract
23P - The correlations between knowledge and attitudes of productive age women toward “SADARI” (breast self-assessment) as early detection of breast cancer in Pejeng Kaja Village, Ubud, Bali
Presenter: Yorky Brahmantya
Session: Poster display session
Resources:
Abstract
24TiP - KEYNOTE-756: A randomized, double-blind, phase III study of pembrolizumab or placebo with neoadjuvant chemotherapy and adjuvant endocrine therapy for high-risk, early-stage, ER+/HER2−breast cancer
Presenter: Fatima Cardoso
Session: Poster display session
Resources:
Abstract