Abstract
Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs) by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer.
Highlights
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer death in the United States
To assess the extent to which in vivo models of patient-derived colorectal cancer explants (PDCEEs) accurately recapitulate and can serve as a model of the human condition, we investigated whether PDCCEs retain key biological features inherent to individual human colorectal cancers (CRC) over time
A number of mouse xenograft models have been established to investigate CRC etiology and treatment. These models have been generated using late passage cell lines derived from human CRCs and while significant treatmentinduced tumor responses have been observed in these models, they are rarely predictive of tumor response in human patients [7]
Summary
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer death in the United States. In 2010, approximately 142,000 people were diagnosed with CRC, and about 40% of these patients presented with advanced disease [1]. In order to improve clinical outcomes and develop new therapeutic approaches, the development of a reliable preclinical model to study CRC biology and drug sensitivities is required. Mouse models of CRC remain one of the most useful tools to decipher the biological mechanisms underlying the oncogenic process. A variety of genetically-engineered, carcinogeninduced and xenograft mouse models have been established [2,3] and it is generally agreed that no one model is sufficient to elucidate all aspects of CRC etiology
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