Abstract 2815: Patient derived orthotopic xenograft (PDOX) model developed from needle biopsy specimen replicated clinical outcomes in advanced pancreatic cancer
Authors: Jeon A-Ra , Choi Sun Il , Park Sang-Jae , Han Sung-Sik , Hong Eun Kyung , Kong Sun-Young , Kim Min Kyeong , Yoon Kyong-Ah , Koh Young-Hwan , Lee Ju Hee , Lee Woo Jin , Kang Young Hwa , Woo Sang Myung , Kim Yun-Hee 
Published: July 2017

Introduction:

A patient-derived xenograft (PDX) as a preclinical model can reflect the pathological and molecular features and drug responsibility of a patient’s tumor. PDXs have been generated by subcutaneously implanting surgically resected tumor fragments into immunodeficient mice. Unfortunately, 80 % of pancreatic cancer patients is unresectable and they show highly aggressive and metastatic tumors. In most cases, diagnoses are confirmed histologically and diagnosed through endoscopic ultrasonography-guided/fine-needle aspiration (EUS/FNA) or percutaneous liver biopsy. However, they are not suitable for subcutaneous implantation into mice due to their threadlike shape and very small size. Therefore, the lack of patient-derived model system in pancreatic cancer is in desperate need of new strategy to cover unresectable patients as well as resectable. Here, we pioneered the development of a unresectable patient-derived orthotopic xenograft (PDOX) model satisfied with short period and high success rate, and made the best use of them as the test model for drug response.

Methods and Results:

PDOX models were established with a technique of direct surgical orthotopic implantation into the pancreatic tail of Athymic nude mice. PDOX models using fine needle biopsy had a higher success rate of engraftment, nearly 40% (17 cases among 44 cases) in patients with a time to progression of &lt;6 months. The histopathological characteristics of the PDOX tumors are similar with those of the patient’s original tissues. Additionally, genetic alterations were retained between patient tissues (F0) and PDOX tumors (F1~F3) from the mutation analysis using a comprehensive cancer panel. For drug responsibility, we selected refractory or sensitive PDOX groups to Gemcitabine and Abraxane based on their clinical information. As results after treatment with Gemcitabine, Abraxane and combination, selected PDOX models showed the drug sensitivity significantly correlated with the drug responsibility of original patients. Tumor growth was monitored by animal MRI every 2 weeks during 2 months. Typically, xenograft models using immortalized pancreatic cancer cell line, CFPAC-1, showed tumor regression to all treatment set.

Conclusion:

Collectively, our PDOX models using needle biopsy specimens can reflect the characteristics of unresectable patients and give the expectation the drug responsibility. They furthermore might be valuable in a screening and development system for targeted therapeutics, which can be applied to a wide range of pancreatic cancer patients.

Citation Format: A-Ra Jeon, Sun Il Choi, Sang-Jae Park, Sung-Sik Han, Eun Kyung Hong, Sun-Young Kong, Min Kyeong Kim, Kyong-Ah Yoon, Young-Hwan Koh, Ju Hee Lee, Woo Jin Lee, Young Hwa Kang, Sang Myung Woo, Yun-Hee Kim. Patient derived orthotopic xenograft (PDOX) model developed from needle biopsy specimen replicated clinical outcomes in advanced pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2815. doi:10.1158/1538-7445.AM2017-2815