Applications of patient-derived tumor xenograft models and tumor organoids

Abstract

Patient-derived tumor xenografts (PDXs), in which tumor fragments surgically dissected from cancer patients are directly transplanted into immunodeficient mice, have emerged as a useful model for translational research aimed at facilitating precision medicine. PDX susceptibility to anti-cancer drugs is closely correlated with clinical data in patients, from whom PDX models have been derived. Accumulating evidence suggests that PDX models are highly effective in predicting the efficacy of both conventional and novel anti-cancer therapeutics. This also allows "coclinical trials," in which pre-clinical investigations in vivo and clinical trials could be performed in parallel or sequentially to assess drug efficacy in patients and PDXs. However, tumor heterogeneity present in PDX models and in the original tumor samples constitutes an obstacle for application of PDX models. Moreover, human stromal cells originally present in tumors dissected from patients are gradually replaced by host stromal cells as the xenograft grows. This replacement by murine stroma could preclude analysis of human tumor-stroma interactions, as some mouse stromal cytokines might not affect human carcinoma cells in PDX models. The present review highlights the biological and clinical significance of PDX models and three-dimensional patient-derived tumor organoid cultures of several kinds of solid tumors, such as those of the colon, pancreas, brain, breast, lung, skin, and ovary.

Oncogenic seRNA functional activation: a novel mechanism of tumorigenesis

“…The remodeled matrix enables melanoma cells to tolerate PLX4720 via stimulating integrin β1/FAK-dependent ERK/MAPK signaling [131]. More importantly, the patient-derived tumor xenografts (PDXs) model revealed that co-inhibition of BRAF and FAK abolishes ERK reactivation in tumor stroma [132].…”

Humanization of Tumor Stroma by Tissue Engineering as a Tool to Improve Squamous Cell Carcinoma Xenograft

“…In this regard, our study aimed to establish an experimental method that focused on the generation of a bioengineered stroma, capable of persisting and sustaining SCC growth. The importance of conditioning the environment for the successful growing of human carcinomas in immunodeficient mice is a very well-known phenomenon [18][19][20]. One of the early observations regarding this issue comes from studies with prostate carcinoma cells LNCaP, which under normal conditions, do not grow in vivo, unless the site of injection is preconditioned by implantation of matrigel or coinjection with human fibroblasts.…”

Radio-Resistance and DNA Repair in Pediatric Diffuse Midline Gliomas

“…Despite the evidence from pre-clinical studies supporting radio-sensitizing strategies, the number of currently active clinical trials exploring the impact of novel agents in combination with IR is limited. Among the reasons that preclude successful translation is the lack of in vivo validation using patient-derived xenograft models, which are more representative of original tumor architecture than commercially available stable cell lines [ 99 ].…”