TY - JOUR
T1 - Targeting signaling pathways in prostate cancer
T2 - mechanisms and clinical trials
AU - He, Yundong
AU - Xu, Weidong
AU - Xiao, Yu Tian
AU - Huang, Haojie
AU - Gu, Di
AU - Ren, Shancheng
N1 - Funding Information:
This work was supported by grants from the Science and Technology Commission of Shanghai Municipality (18410750200 to R.S.), National Natural Science Foundation of China (82125025 to R.S., 81872105 to R.S.), and National Major R&D Program (2017YFC0908002).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Prostate cancer (PCa) affects millions of men globally. Due to advances in understanding genomic landscapes and biological functions, the treatment of PCa continues to improve. Recently, various new classes of agents, which include next-generation androgen receptor (AR) signaling inhibitors (abiraterone, enzalutamide, apalutamide, and darolutamide), bone-targeting agents (radium-223 chloride, zoledronic acid), and poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib, rucaparib, and talazoparib) have been developed to treat PCa. Agents targeting other signaling pathways, including cyclin-dependent kinase (CDK)4/6, Ak strain transforming (AKT), wingless-type protein (WNT), and epigenetic marks, have successively entered clinical trials. Furthermore, prostate-specific membrane antigen (PSMA) targeting agents such as 177Lu-PSMA-617 are promising theranostics that could improve both diagnostic accuracy and therapeutic efficacy. Advanced clinical studies with immune checkpoint inhibitors (ICIs) have shown limited benefits in PCa, whereas subgroups of PCa with mismatch repair (MMR) or CDK12 inactivation may benefit from ICIs treatment. In this review, we summarized the targeted agents of PCa in clinical trials and their underlying mechanisms, and further discussed their limitations and future directions.
AB - Prostate cancer (PCa) affects millions of men globally. Due to advances in understanding genomic landscapes and biological functions, the treatment of PCa continues to improve. Recently, various new classes of agents, which include next-generation androgen receptor (AR) signaling inhibitors (abiraterone, enzalutamide, apalutamide, and darolutamide), bone-targeting agents (radium-223 chloride, zoledronic acid), and poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib, rucaparib, and talazoparib) have been developed to treat PCa. Agents targeting other signaling pathways, including cyclin-dependent kinase (CDK)4/6, Ak strain transforming (AKT), wingless-type protein (WNT), and epigenetic marks, have successively entered clinical trials. Furthermore, prostate-specific membrane antigen (PSMA) targeting agents such as 177Lu-PSMA-617 are promising theranostics that could improve both diagnostic accuracy and therapeutic efficacy. Advanced clinical studies with immune checkpoint inhibitors (ICIs) have shown limited benefits in PCa, whereas subgroups of PCa with mismatch repair (MMR) or CDK12 inactivation may benefit from ICIs treatment. In this review, we summarized the targeted agents of PCa in clinical trials and their underlying mechanisms, and further discussed their limitations and future directions.
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U2 - 10.1038/s41392-022-01042-7
DO - 10.1038/s41392-022-01042-7
M3 - Review article
C2 - 35750683
AN - SCOPUS:85132851356
SN - 2095-9907
VL - 7
JO - Signal Transduction and Targeted Therapy
JF - Signal Transduction and Targeted Therapy
IS - 1
M1 - 198
ER -