Novel Patient-Derived CTC-Xenograft Models for the Study of Pancreatic Cancer Biology, Metastasis and Therapy

Introduction

 

Pancreatic cancer is highly malignant and has the lowest survival rate of any human cancer. Multiple clinical trials addressing pancreatic cancer failed to show significant success during the past decade. Extensive metastasis and therapeutic resistance are two major contributors of poor prognosis, and their mechanisms are largely unknown.  Circulating tumor cells (CTC) are a metastatic cancer cell type readily available in clinical blood samples. CTC are in dynamic equilibrium with tumor cells at the primary and metastatic sites, thus reflecting the state of the in-situ tumor in real time. Therefore, patient-derived CTC-xenograft model (CTC-PDX) can serve as a patient cancer surrogate, which provides a unique opportunity for investigations at personal oncology level.

 

Technology Description

 

Developing a reproducible CTC-patient derived xenograft (CTC-PDX) model is challenging due to the rarity of CTC in blood samples. Dr. Chung’s laboratory has extensive experience studying cancer growth, invasion, and metastasis. The inventors have developed a cost-effective protocol to expand patient-derived CTC with significantly improved success rate and highly reproducible CTC-xenograft mouse models. The inoculated tumors show rapid growth and widespread metastasis, and they exhibit features of the original tumor, making this the first CTC-PDX model that can grow and metastasize in mice. In addition, the xenograft model has been applied successfully to test the sensitivity to anti-tumor agents.

 

Stage of Development

 

Preclinical; in-vivo data available.

 

Advantages/Novelty

 

The CTC expansion protocol:

•       Is a cost-effective method requiring no artificial additives

•       Has highly improved success rate and reproducibility compared to existing methods

The CTC-PDX model:

•       Is a highly reproducible model to show tumor growth and metastasis

 

Applications

 

The ex-vivo expanded patient-derived CTC and CTC-PDX mouse model can be used as:

•       a surrogate of the patient cancer for driving mutation analysis, malignancy and metastatic potential

•       a subject for anti-cancer drug screening and to study drug resistance

•       a research subject for biomarker identification for cancer diagnosis and prognosis

•       a research subject for tumor formation, progression, invasion

•       a model to evaluate new therapeutics and imaging modalities

 

Intellectual Property

 

•       PCT application PCT/US2016/060646 filed.

 

Patent Information:
Category(s):
Tool
For Information, Contact:
Wenyue Du
Associate - IP Management & Licensing
310-423-2241
wenyue.du@cshs.org
Inventors:
Leland Chung
Ruoxiang Wang
Keywords:
Oncology