Androgen deprivation therapy (ADT) is a usual first-line option for males with advanced prostate cancer, but the vast majority eventually progress while receiving ADT, and the disease state is referred to as castration-resistant prostate cancer (CRPC). The mechanisms driving progression from androgen-dependent (hormone-sensitive or castration-sensitive) prostate cancer to CRPC are still largely unclear. However, continued androgen receptor signaling, despite depletion of circulating androgens and androgen receptor blockade, is thought to be central to the development of CRPC.
Aldo-keto reductase family 1 member C3 (AKR1C3) is an enzyme in the steroidogenesis pathway, especially in the formation of testosterone and dihydrotestosterone, and is believed to have a key role in promoting prostate cancer (PCa) progression, particularly in castration-resistant prostate cancer (CRPC). It participates in epigenetic regulation and ferroptosis in prostate cancer, and expression of AKR1C3 is higher in metastatic and CRPC tissues than in normal prostate tissues or benign prostatic hyperplasia, or localized prostate cancer. AKR1C3 upregulation could be a potential adaptive mechanism for ADT and a good candidate as a CRPC biomarker. However, a major bottleneck for novel biomarkers in CRPC, including AKR1C3, is the dependency on repeated biopsies.
Exosomes are cell-derived compartments that participate in many biological processes. Cancer cell-manufactured exosomes are critical mediators of intercellular communication, thus playing a significant role in tumor progression. They can be detected in the early stage of disease, before prostate-specific antigen (PSA) elevation, metastatic symptoms, or some tissue marker positivity. Plasma AKR1C3-EXO is associated with patient prognosis regarding overall survival and progression-free survival under first-line abiraterone use. Plasma AKR1C3-EXO can be used as a biomarker in metastatic castration-resistant prostate cancer.
HUABIO Antibody Used: CD9 RECOMBINANT RABBIT MONOCLONAL ANTIBODY [SA35-08] (ET1601-9)
This study by Zhu, Sha, et al., investigates the prognostic and predictive value of AKR1C3 level in paired plasma exosomes and tissue samples from a group of prospectively recruited patients with metastatic castration-resistant prostate cancer (mCRPC).
Researchers at the Institute of Urology used HUABIO’s CD9 RECOMBINANT RABBIT MONOCLONAL ANTIBODY [SA35-08] (ET1601-9) in western blot analysis to characterize exosomes. Researchers characterized the exosomes by multiple complementary techniques, including NTA, western blot, and electron microscope.
A simple blood-based test of exosomal AKR1C3 can provide significant clues for patient management and prognosis. Plasma AKR1C3-EXO is associated with patient prognosis regarding OS and ABI-PFS and can be used as a biomarker in mCRPC.
References: Zhu, Sha, et al. "Plasma Exosomal AKR1C3 mRNA Expression Is a Predictive and Prognostic Biomarker in Patients with Metastatic Castration-Resistant Prostate Cancer." The Oncologist (2022).