#0404
Establishment of Two Cases of PDX from Organoids Derived from CTCs Collected from Prostate Cancer Patient's blood
K. Hikami1, T. Sunada2, K. Hattahara1, M. Fujiwara1, A. Fukunaga1, K. Mizuno1, T. Sumiyoshi1, T. Goto1, S. Akamatsu3, T. Kobayashi1
1Kyoto
University Graduate School of Medicine, Department of Urology, Kyoto city,
Japan
2Kurashiki Central Hospital, Department of Urology, Kurashiki city,
Japan
3Nagoya University Graduate School of Medicine, Department of
Urology, Nagoya city, Japan
Introduction:
The treatment landscape of metastatic castration-sensitive prostate cancer (mCSPC) has expanded since the introduction of androgen receptor signaling inhibitors (ARSI) and docetaxel in combination with androgen deprivation therapy (ADT). However, the progression to castration-resistant prostate cancer (CRPC) remains inevitable. Ideally, multiple metastatic tumor biopsies across the clinical course are reasonable to elucidate resistance to systemic therapies or explore novel treatment targets. However, many patients do not have accessible metastatic lesions. To overcome this limitation, we aimed to establish patient-derived xenografts(PDXs) from circulating tumor cells (CTCs) as an experimental model.
Material and methods:
CTCs were isolated by removing white blood cells from whole blood using anti-CD15 and anti-CD45 antibody. The extracted CTC solution was mixed with Matrigel at a 1:4 ratio and plated onto a dome shape in a 24-well plate to create organoids. Organoids were maintained in a 37℃ incubator. After approximately 2 weeks, organoids were subcutaneously implanted into NOD/SCID mice to establish PDX models.
Results:
We made PDX from the organoids of isolated CTCs from 10 blood samples of 6 patients with mCSPC or mCRPC. Two PDX models were successfully established using CTCs collected from one patient before and after treatment with ADT plus abiraterone. Hematoxylin and eosin staining revealed that the morphology of the two tumor tissues obtained from the PDX model was prostatic adenocarcinoma. Immunohistochemistry revealed that the two tumor tissues expressed AR, PSA, and NKX3.1. Interestingly, western blotting showed that one tumor tissue of PDX collected after ADT plus abiraterone had different molecular weights of the AR protein, indicating the presence of AR variants.