期刊
CANCER CELL
卷 38, 期 2, 页码 279-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2020.06.005
关键词
-
资金
- National Cancer Institute [R01CA155169-04, R01CA19387-01, R01 CA166413, R01 CA204232, R00CA218885-04, P30CA008748, U54OD020355]
- Howard Hughes Medical Institute [DT0712]
- NIH/NCI/MSKCC Spore in Prostate Cancer [P50 CA092629-14]
- NCI/MSKCC Support Grant/Core Grant [P30CA008748-49, P3CA008748-49-S2]
- Starr Cancer Consortium [I9-A9-071]
- Department of Defense [PC170900, W81XWH-18-1-0379]
- Cancer Prevention Research Institute (CPRIT) [RR170050, RP150596]
- Vallee Foundation
- Prostate Cancer Foundation [17YOUN12, 17YOUN10, 18YOUNG24]
- Dutch Cancer Foundation
- Welch Foundation [I-2005-20190330]
- WorldQuant Foundation
- Pershing Square Sohn Cancer Research Alliance
- NIH [1R01MH117406]
- UTSW
- UTSW Harold C. Simmons Cancer Center Pilot Award, USA
- NCI [F99CA223063]
Despite the development of second-generation antiandrogens, acquired resistance to hormone therapy remains a major challenge in treating advanced prostate cancer. We find that cancer-associated fibroblasts (CAFs) can promote antiandrogen resistance in mouse models and in prostate organoid cultures. We identify neuregulin 1 (NRG1) in CAF supernatant, which promotes resistance in tumor cells through activation of HER3. Pharmacological blockade of the NRG1/HER3 axis using clinical-grade blocking antibodies re-sensitizes tumors to hormone deprivation in vitro and in vivo. Furthermore, patients with castration-resistant prostate cancer with increased tumor NRG1 activity have an inferior response to second-generation antiandrogen therapy. This work reveals a paracrine mechanism of antiandrogen resistance in prostate cancer amenable to clinical testing using available targeted therapies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据