In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 1058-1058
Abstract:
Background: Primary liver cancer (PLC) is the second cause of cancer-related mortality worldwide and includes mainly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Due to the limited treatment options and diversity of subtypes there is an unmet need to develop novel clinical approach to capture tumor heterogeneity and to guide personalized therapy in PLC. Methods: 33 surgically resected PLC patient tissues were cultured for organoid models. Patient-derived organoids (PDOs) and matched primary tumors were molecularly characterized by whole exome sequencing (WES) and RNA sequencing (RNA-seq). Subset of PDOs were screened for sensitivity to clinical medication recommended by National Comprehensive National network (NCCN) guideline to evaluate the feasibility of PLC-derived organoids in drug testing. Results:11 HCC, 1 ICC and 2 neuroendocrine tumors from patients were successfully established for organoid models. The success rate for generation of PLC organoids was 42.4% (14/33). To investigate whether organoids preserved the molecular characteristics of the originating tumors, 14 matched tumor-organoid pairs of genomic profile concordance and 3 pairs of gene expression profiles were analyzed based on WES and RNA-seq, respectively. Of the total somatic mutations found in the tumor tissues, a median of 55.5% (range 12.5% - 92.9%) mutations was observed in the corresponding PLC organoids. TP53 was the most common mutated gene either in tumors or in the organoids, with the same mutational frequency of 71.4% (10/14). Gene expression of organoids were highly correlated with their matched parental tumor tissue (median Spearman's correlation coefficient r = 0.81, range 0.76 - 0.85). To investigate the utility of PLC organoids for drug screening, multiple anti-cancer compounds (n=6-9) in standard clinical care were tested in 5 organoids which were showed high genomic concordance with their originating tumors. A good consistency between the drug screening and validation results was observed on patient NO.43 with ICC. The organoid of NO.43 was most sensitive to combined chemotherapy of irinotecan plus cisplatin. Together with drug testing result and clinical practice guidelines, this ICC patient was treated with irinotecan plus cisplatin after surgery and demonstrated durable response in clinical. In one-year follow-up no sign of recurrence was observed. Conclusion: PLC organoids intermediately to highly recapitulates the molecular and biological features of tumors. Drug sensitivity testing on PLC organoid models have the potential to guide personalized treatment in the clinical setting. Citation Format: Jianhua Rao, Feng Cheng, Long Zhang, Xiaohu Sun, Chao Song, Xuejiao Ma, Lei Ye, Wanglong Deng, Yansong Li, Zaozao Chen. Establishment of patient-derived organoid models of primary liver cancer and enable clinical personalized oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1058.
Type of Medium:
Online Resource
ISSN:
1538-7445
DOI:
10.1158/1538-7445.AM2023-1058
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2023
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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