Tumor-derived OBP2A promotes prostate cancer castration resistance
Abstract
Androgen deprivation therapy (ADT) is a systemic therapy for advanced prostate cancer (PCa); although most patients initially respond to ADT, almost all cancers eventually develop castration-resistant PCa (CRPC). Currently, most research focuses on castration-resistant tumors, and the role of tumors in remission is almost completely ignored. Here, we report that odorant-binding protein (OBP2A) released from tumors in remission during ADT catches survival factors, such as CXCL15/IL8, to promote PCa cell androgen-independent growth and enhance the infiltration of myeloid-derived suppressor cells (MDSCs) into tumor microenvironment, leading to the emergence of castration resistance. OBP2A knockdown significantly inhibits CRPC and metastatic CRPC development and improves therapeutic efficacy of CTLA-4/PD-1 antibodies. Treatment with OBP2A-binding ligand α-pinene interrupts the function of OBP2A and suppresses CRPC development. Furthermore, α-pinene–conjugated doxorubicin/docetaxel can be specifically delivered to tumors, resulting in improved anticancer efficacy. Thus, our studies establish a novel concept for the emergence of PCa castration resistance and provide new therapeutic strategies for advanced PCa.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 22, 2022
- Source ID
- 10.1084/jem.20211546
Entities
People
- Changhao Huang
- Fuzhuo Li
- HaJeung Park
- Jasreman Dhillon
- Ji-Hak Jeong
- Jun-Li Luo
- Qingqing Liu
- Shangwei Zhong
- Shoujiao Peng
- Xueyan Chen
- You Mie Lee
Organizations
- Cancer Research Institute
- H. Lee Moffitt Cancer Center & Research Institute
- Kyungpook National University
- National Institutes of Health
- Scripps Research
- United States Department of Defense