Establishment, characterization, and biobanking of 36 pancreatic cancer organoids: prediction of metastasis in resectable pancreatic cancer

Soon-Chan Kim ^1,2, Ha-Young Seo ¹, Ja-Oh Lee ¹

¹Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
²Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.
³Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
⁴Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea. gidoctor@snu.ac.kr.
⁵Department of Surgery, Seoul National University College of Medicine, 103, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea. jangjy4@snu.ac.kr.
⁶Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Korea. kujalok@snu.ac.kr.
⁷Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea. kujalok@snu.ac.kr.
⁸Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea. kujalok@snu.ac.kr.

⁰Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Cellular Oncology (dordrecht, Netherlands) +

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April 15, 2024

View abstract on PubMed

Summary

Understanding pancreatic ductal adenocarcinoma (PDAC) metastasis is key. Molecular analysis of borderline resectable PDAC organoids reveals distinct patterns linked to metastatic potential and drug response.

Area Of Science

Oncology
Molecular Biology
Cancer Research

Background

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to early dissemination, limiting treatment options.
Metastatic clones often cause treatment failure and distant metastasis in PDAC patients.
Understanding the molecular basis of PDAC dissemination is crucial for improving patient outcomes.

Purpose Of The Study

To elucidate the molecular architecture of borderline resectable PDAC.
To identify factors contributing to cancer dissemination in PDAC.
To correlate molecular profiles with metastatic potential in PDAC.

Main Methods

Generation of 36 organoids from primary PDAC tumors with varying metastatic status.
Comprehensive analysis using whole-exome sequencing and RNA sequencing.
Assessment of drug responses to 18 clinically relevant compounds.

Main Results

Borderline resectable PDAC organoids showed distinct molecular patterns based on metastatic capability.
Genetic and transcriptional factors were identified as key indicators of metastatic potency.
Significant variations in drug responses were observed among organoids with different metastatic potentials.

Conclusions

Molecular composition and drug response patterns can identify metastatic PDAC.
Integrating these factors aids in understanding and potentially predicting PDAC dissemination.
This approach may inform personalized treatment strategies for PDAC.

Keywords:

Biobank Metastasis Organoid Pancreatic adenocarcinoma Prediction model