A Biobank of Colorectal Cancer Patient-Derived Xenografts

Abstract

Colorectal cancer (CRC) is a challenging disease, with a high mortality rate and limited effective treatment options, particularly for late-stage disease. Patient-derived xenografts (PDXs) have emerged as an informative, renewable experimental resource to model CRC architecture and biology. Here, we describe the generation of a biobank of CRC PDXs from stage I to stage IV patients. We demonstrate that PDXs within our biobank recapitulate the histopathological and mutation features of the original patient tumor. In addition, we demonstrate the utility of this resource in pre-clinical chemotherapy and targeted treatment studies, highlighting the translational potential of PDX models in the identification of new therapies that will improve the overall survival of CRC patients.

Establishment of a Patient-Derived Xenograft Model of Colorectal Cancer in CIEA NOG Mice and Exploring Smartfish Liquid Diet as a Source of Omega-3 Fatty Acids

“…Hence, a longer latency time may increase the engraftment rate. In line with our findings, a recent study by Abdirahman et al also reported an allowed six month latency period until established CRC PDX growth [ 19 ], and Chijiwa et al stated that animals were sacrificed as “failed” if mice did not develop PDX growth over six months from engraftment [ 21 ].…”

“…PDXs preserve the biological characteristics of tumors better than CDX models, and therefore serve as a better research model for personalized cancer treatment. PDXs with established growth may be considered first generation xenografts, while several studies have made PDX lines (third generation PDX) stored in a PDX line biobank for future studies [ 19 ]. By using first generation xenografts there is a risk of failure to establish growth, while growth has already been confirmed with second or third generation PDX lines.…”

The HROC-Xenobank—A High Quality Assured PDX Biobank of >100 Individual Colorectal Cancer Models

“…Further, the HROC PDX models precisely recapitulated the mutation profiles of the original patient tumors, thereby confirming previous data [32,38,39]. In particular, our study pointed out that pathogenic or likely pathogenic mutations detected in the original tumors were maintained in the PDX tumors.…”

“…Comparative pathomorphological analysis and genetic identity testing confirmed the close proximity of the HROC-Xenobank models to the original patient tumors. Moreover, we could confirm previous findings that PDX models, in the majority of cases, maintain the original tumor’s biological features [ 2 , 3 , 32 ]. For each individual HROC PDX model we described in detail, the pathomorphological structures were reproduced from the original patient tumor.…”

“…Abdirahman et al reported an engraftment success of 22/33 (67%) cases for their CRC PDX series, but because four cases turned out to be human lymphomas, their rate dropped to 18/33 (55%) [ 32 ]. Their lymphoma rate was surprisingly high (4/22; 18.2%).…”