Interview Seminar

Title：From Disease in 3D Organoids to Clinical Trial: A New Type of Candidate for Cancer Researches and Stem Cell Studies of Prostate

Speaker: Dr. Dong GAO, Ph.D.

Memorial Sloan Kettering Cancer Center

Time: 4:00pm, April 23rd

Venue: Rm. 411, New Life Sciences Building

In the past few years, we have witnessed a rapid growth in the number of clinically approved agents that prolong survival and in the number of novel promising targets in the treatment of advanced prostate cancer. However, each of these agents only benefits a subset of patients and predicative biomarkers that help patient selection are urgently needed. In the majority of other cancer types, validated biomarkers have been discovered using in vitro models. However, prostate cancer is hampered by the lack of in vitro models that recapitulate the diversity of the disease. To address these limitations, we have optimized 3D culture conditions that generate "organoids" of metastatic prostate cancer from biopsy samples. The first seven fully characterized organoid lines recapitulate the molecular diversity of prostate cancer subtypes, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression, and CHD1 loss. Whole-exome sequencing shows a low mutational burden, consistent with genomics studies, but with mutations in FOXA1 and PIK3R1, as well as in DNA repair and chromatin modifier pathways that have been reported in advanced disease. The organoid culture system should enable the generation of a large repertoire of patient-derived prostate cancer lines amenable to genetic and pharmacologic studies.

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