Extracellular Matrix in Synthetic Hydrogel-Based Prostate Cancer Organoids Regulate Therapeutic Response to EZH2 and DRD2 Inhibitors

Extracellular Matrix in Synthetic Hydrogel-Based Prostate Cancer Organoids Regulate Therapeutic Response to EZH2 and DRD2 Inhibitors

© 2021 Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 34(2022), 2 vom: 05. Jan., Seite e2100096
1. Verfasser: Mosquera, Matthew J (VerfasserIn)
Weitere Verfasser: Kim, Sungwoong, Bareja, Rohan, Fang, Zhou, Cai, Shuangyi, Pan, Heng, Asad, Muhammad, Martin, Maria Laura, Sigouros, Michael, Rowdo, Florencia M, Ackermann, Sarah, Capuano, Jared, Bernheim, Jacob, Cheung, Cynthia, Doane, Ashley, Brady, Nicholas, Singh, Richa, Rickman, David S, Prabhu, Varun, Allen, Joshua E, Puca, Loredana, Coskun, Ahmet F, Rubin, Mark A, Beltran, Himisha, Mosquera, Juan Miguel, Elemento, Olivier, Singh, Ankur
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2022
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article chemoresistance dopamine receptors epigenetics neuroendocrine tumor microenvironment Androgen Receptor Antagonists DRD2 protein, human DRD2 protein, mouse Hydrogels mehr... Receptors, Dopamine D2 EZH2 protein, human EC 2.1.1.43 Enhancer of Zeste Homolog 2 Protein
LEADER 01000naa a22002652 4500
001 NLM332170802
003 DE-627
005 20231225215039.0
007 cr uuu---uuuuu
008 231225s2022 xx |||||o 00| ||eng c
024 7 |a 10.1002/adma.202100096  |2 doi 
028 5 2 |a pubmed24n1107.xml 
035 |a (DE-627)NLM332170802 
035 |a (NLM)34676924 
040 |a DE-627  |b ger  |c DE-627  |e rakwb 
041 |a eng 
100 1 |a Mosquera, Matthew J  |e verfasserin  |4 aut 
245 1 0 |a Extracellular Matrix in Synthetic Hydrogel-Based Prostate Cancer Organoids Regulate Therapeutic Response to EZH2 and DRD2 Inhibitors 
264 1 |c 2022 
336 |a Text  |b txt  |2 rdacontent 
337 |a ƒaComputermedien  |b c  |2 rdamedia 
338 |a ƒa Online-Ressource  |b cr  |2 rdacarrier 
500 |a Date Completed 31.03.2022 
500 |a Date Revised 02.01.2023 
500 |a published: Print-Electronic 
500 |a Citation Status MEDLINE 
520 |a © 2021 Wiley-VCH GmbH. 
520 |a 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 regulates the response to small-molecule inhibitors of epigenetic targets and Dopamine Receptor D2 (DRD2), the latter being an understudied target in neuroendocrine tumors. In vivo patient-derived xenograft in immunocompromised mice showed strong anti-tumor response when treated with a DRD2 inhibitor. Finally, we demonstrate that therapeutic response in CRPC-NEPCs under drug-resistant ECM conditions can be overcome by first cellular reprogramming with epigenetic inhibitors, followed by DRD2 treatment. The synthetic organoids suggest the regulatory role of ECM in therapeutic response to targeted therapies in CRPC-NEPCs and enable the discovery of therapies to overcome resistance 
650 4 |a Journal Article 
650 4 |a chemoresistance 
650 4 |a dopamine receptors 
650 4 |a epigenetics 
650 4 |a neuroendocrine 
650 4 |a tumor microenvironment 
650 7 |a Androgen Receptor Antagonists  |2 NLM 
650 7 |a DRD2 protein, human  |2 NLM 
650 7 |a DRD2 protein, mouse  |2 NLM 
650 7 |a Hydrogels  |2 NLM 
650 7 |a Receptors, Dopamine D2  |2 NLM 
650 7 |a EZH2 protein, human  |2 NLM 
650 7 |a EC 2.1.1.43  |2 NLM 
650 7 |a Enhancer of Zeste Homolog 2 Protein  |2 NLM 
650 7 |a EC 2.1.1.43  |2 NLM 
700 1 |a Kim, Sungwoong  |e verfasserin  |4 aut 
700 1 |a Bareja, Rohan  |e verfasserin  |4 aut 
700 1 |a Fang, Zhou  |e verfasserin  |4 aut 
700 1 |a Cai, Shuangyi  |e verfasserin  |4 aut 
700 1 |a Pan, Heng  |e verfasserin  |4 aut 
700 1 |a Asad, Muhammad  |e verfasserin  |4 aut 
700 1 |a Martin, Maria Laura  |e verfasserin  |4 aut 
700 1 |a Sigouros, Michael  |e verfasserin  |4 aut 
700 1 |a Rowdo, Florencia M  |e verfasserin  |4 aut 
700 1 |a Ackermann, Sarah  |e verfasserin  |4 aut 
700 1 |a Capuano, Jared  |e verfasserin  |4 aut 
700 1 |a Bernheim, Jacob  |e verfasserin  |4 aut 
700 1 |a Cheung, Cynthia  |e verfasserin  |4 aut 
700 1 |a Doane, Ashley  |e verfasserin  |4 aut 
700 1 |a Brady, Nicholas  |e verfasserin  |4 aut 
700 1 |a Singh, Richa  |e verfasserin  |4 aut 
700 1 |a Rickman, David S  |e verfasserin  |4 aut 
700 1 |a Prabhu, Varun  |e verfasserin  |4 aut 
700 1 |a Allen, Joshua E  |e verfasserin  |4 aut 
700 1 |a Puca, Loredana  |e verfasserin  |4 aut 
700 1 |a Coskun, Ahmet F  |e verfasserin  |4 aut 
700 1 |a Rubin, Mark A  |e verfasserin  |4 aut 
700 1 |a Beltran, Himisha  |e verfasserin  |4 aut 
700 1 |a Mosquera, Juan Miguel  |e verfasserin  |4 aut 
700 1 |a Elemento, Olivier  |e verfasserin  |4 aut 
700 1 |a Singh, Ankur  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Advanced materials (Deerfield Beach, Fla.)  |d 1998  |g 34(2022), 2 vom: 05. Jan., Seite e2100096  |w (DE-627)NLM098206397  |x 1521-4095  |7 nnns 
773 1 8 |g volume:34  |g year:2022  |g number:2  |g day:05  |g month:01  |g pages:e2100096 
856 4 0 |u http://dx.doi.org/10.1002/adma.202100096  |3 Volltext 
912 |a GBV_USEFLAG_A 
912 |a SYSFLAG_A 
912 |a GBV_NLM 
912 |a GBV_ILN_350 
951 |a AR 
952 |d 34  |j 2022  |e 2  |b 05  |c 01  |h e2100096