作者
Matthew J Mosquera, Sungwoong Kim, Rohan Bareja, Zhou Fang, Shuangyi Cai, Heng Pan, Muhammad Asad, Maria Laura Martin, Michael Sigouros, Florencia M Rowdo, Sarah Ackermann, Jared Capuano, Jacob Bernheim, Cynthia Cheung, Ashley Doane, Nicholas Brady, Richa Singh, David S Rickman, Varun Prabhu, Joshua E Allen, Loredana Puca, Ahmet F Coskun, Mark A Rubin, Himisha Beltran, Juan Miguel Mosquera, Olivier Elemento, Ankur Singh
发表日期
2022/1
期刊
Advanced Materials
卷号
34
期号
2
页码范围
2100096
简介
Following treatment with androgen receptor (AR) pathway inhibitors, ≈20% of prostate cancer patients progress by shedding their AR‐dependence. These tumors undergo epigenetic reprogramming turning castration‐resistant prostate cancer adenocarcinoma (CRPC‐Adeno) into neuroendocrine prostate cancer (CRPC‐NEPC). No targeted therapies are available for CRPC‐NEPCs, and there are minimal organoid models to discover new therapeutic targets against these aggressive tumors. Here, using a combination of patient tumor proteomics, RNA sequencing, spatial‐omics, and a synthetic hydrogel‐based organoid, putative extracellular matrix (ECM) cues that regulate the phenotypic, transcriptomic, and epigenetic underpinnings of CRPC‐NEPCs are defined. Short‐term culture in tumor‐expressed ECM differentially regulated DNA methylation and mobilized genes in CRPC‐NEPCs. The ECM type distinctly …
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MJ Mosquera, S Kim, R Bareja, Z Fang, S Cai, H Pan… - Advanced Materials, 2022