Development of an in vivo syngeneic mouse transplant model of invasive intestinal adenocarcinoma driven by endogenous expression of Pik3caH1047R and Apc loss

de Las Heras, F; Mitchell, CB; Murray, WK; Clemons, NJ; Phillips, WA

Author(s): de Las Heras, F; Mitchell, CB; Murray, WK; Clemons, NJ; Phillips, WA;
Details: Publication Year 2024,Volume 19,Issue #8,Page e0308051
Journal Title: PLOS One
Publication Type: Research article
Abstract: Preclinical models that replicate patient tumours as closely as possible are crucial for translational cancer research. While in vitro cancer models have many advantages in assessing tumour response therapy, in vivo systems are essential to enable evaluation of the role of the tumour cell extrinsic factors, such as the tumour microenvironment and host immune system. The requirement for a functional immune system is particularly important given the current focus on immunotherapies. Therefore, we set out to generate an immunocompetent, transplantable model of colorectal cancer suitable for in vivo assessment of immune-based therapeutic approaches. Intestinal tumours from a genetically engineered mouse model, driven by expression of a Pik3ca mutation and loss of Apc, were transplanted into wild type C57BL/6 host mice and subsequently passaged to form a novel syngeneic transplant model of colorectal cancer. Our work confirms the potential to develop a panel of mouse syngeneic grafts, akin to human PDX panels, from different genetically engineered, or carcinogen-induced, mouse models. Such panels would allow the in vivo testing of new pharmaceutical and immunotherapeutic treatment approaches across a range of tumours with a variety of genetic driver mutations.
Publisher: PLOS
Keywords: Animals; *Class I Phosphatidylinositol 3-Kinases/genetics/metabolism; Mice; *Adenocarcinoma/genetics/pathology; *Disease Models, Animal; *Mice, Inbred C57BL; Intestinal Neoplasms/genetics/pathology; Adenomatous Polyposis Coli Protein/genetics; Phosphatidylinositol 3-Kinases/metabolism; Transplantation, Isogeneic; Mutation; Humans; Colorectal Neoplasms/genetics/pathology
Department(s): Laboratory Research; Pathology
Publisher's Version: https://doi.org/10.1371/journal.pone.0308051
Open Access at Publisher's Site: https://doi.org/10.1371/journal.pone.0308051
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-08-29 01:38:18

Last Modified: 2024-08-29 01:48:55