Tumor-derived OBP2A promotes prostate cancer castration resistance
The Journal of experimental medicine(2022)
摘要
This study unveils that OBP2A from PCa in remission during ADT enhances PCa growth and MDSCs infiltration through interaction with CXCL15/IL8, leading to CRPC emergence. Targeting OBP2A of tumor in remission would be effective therapeutic strategy for advanced PCa. 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 alpha-pinene interrupts the function of OBP2A and suppresses CRPC development. Furthermore, alpha-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.
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关键词
prostate cancer,obp2a,tumor-derived
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