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Patient-derived organoid systems for the study of castrate-resistant metastatic prostate cancer

Abstract

Bone metastases of prostate cancer continue to elude effective clinical management world-wide. A newly developed xenograft model, PCSD1, is a pre-clinical therapeutic development and testing platform to understand the mechanisms of resistance to androgen deprivation therapy of bone metastatic prostate cancer. Prostate cancer is a heterogeneous disease for which it is especially important to study models that represent the range of different patients. However, of the patient samples investigated by Christina Jamieson’s lab at UCSD, only 5 out of 20 (25%) were able to successfully create xenografts. The hypothesis I tested is that metastatic cells that have failed to xenograft into a patient-derived tumor xenograft mouse model will be able to successfully survive in vitro in an organoid culture system. The goals of my research were twofold: to successfully develop organoid cultures for both cells that have successfully and unsuccessfully xenografted into the mouse model and to perform imaging and genetic analysis on these organoids.

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