214P - Establishment of colon cancer liver metastasis PDTX model for the evaluation of chemotherapy

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cytotoxic agents
Hepatobiliary Cancers
Translational Research
Presenter Seohee Choi
Citation Annals of Oncology (2016) 27 (suppl_9): ix53-ix67. 10.1093/annonc/mdw581
Authors S. Choi1, J.S. Park1, J. Jung2, D.S. Yoon1
  • 1Surgery, Yonsei Cancer Center Yonsei University, 06273 - Seoul/KR
  • 2College Of Pharmacy, Duksung Women’s University, 01369 - Seoul/KR

Abstract

Background

Colorectal cancer (CRC) often leads to secondary liver metastasis. To predict chemotherapeutic efficacy, an animal model that preserves the physiological properties of patients’ tumors should be established, and this might be achieved using a patient-derived tumor xenograft (PDTX) model that maintain tumor histopathological architecture. The purpose of this study was to characterize the histological and genomic fidelities of CRC-liver metastasis PDTX models and to evaluate the possibility of CRC-liver metastasis PDTX models for development of patient tailored chemotherapy.

Methods

Tissue obtained from a CRC-liver metastasis patient (F0) was transplanted into a subcutaneous pocket in a non-obese diabetic (NOD)/severe combined immune deficiency (SCID) female mouse (F1). Tumor tissue incubated in NOD/SCID mouse was collected and re-transplanted into nude mice (F2). When tumor volumes reached ∼ 500 mm3, F2 mice were randomly divided up into 4 groups (n = 4), that is, a doxorubicin, cisplatin, docetaxel and a non-treated control group. Tumor growths were determined, and tumor tissues were investigated by H&E staining, TUNEL assay, and immunohistochemistry. To determine where mutant allele frequencies vary between different passages, we performed gene mutations in these PDTx and their paired primary tumors by ultra-deep exam sequencing on cancer related genes.

Results

Tumorigenesis in the PDTX model (F2) took about 3 weeks. Tumor physiological properties were consistent with those of the patient’s tumors. Anticancer drugs delayed tumor growth, inhibited proliferation, and caused apoptosis. Docetaxel was more effective than the other anticancer drugs. Target exon sequencing analysis showed that there were some genetic variations in 83 cancer related genes across generation. But the prognostic impact of colon cancer mutation profiling EGFR, KRAS, BRAF, PIK3CA, NRAS, APC and TP53 showed the same mutations in paired tumors. This result indicates that mutational changes in PDTX were preserved at lest in the early passages in mice.

Conclusions

A CRC liver metastasis PDTX model was established. This model retained the physiological characters of the patient’s tumor and might provide a powerful means for assessing chemotherapeutic efficacy.

Clinical trial indentification

Legal entity responsible for the study

Park

Funding

Park

Disclosure

All authors have declared no conflicts of interest.