The Kaplan-Meier method was used to evaluate time to event outcomes: time to development of metastatic disease, time to development of castration resistance, and time to prostate-specific antigen (PSA) progression after first-line androgen receptor pathway inhibitor (ARPI) therapy in a patient subset.
We searched multiple databases and abstracts of major meetings up to June 2019 for randomised trials of patients receiving first-line therapy for metastatic disease, a combination of ADT and one (or more) of taxane-based chemotherapy, and androgen receptor-targeted therapies.
Together, these results provide the first detailed mechanism of how the AR can differentially alter PCa and BCa metastasis; thus, targeting the newly identified AR-miR-525-5p-SLPI axis may help suppress metastasis.
Nevertheless, the overall concordance of 60% of AR expression in primary tumor and metastasis implies that a clinician who need the AR value to give anti-AR therapy should have the data on both the tumor materials.
Recent findings unmasked the importance of androgen receptor (AR) signaling in regulation of DNA repair, and alterations of the AR-DNA repair factor axis were shown to promote aggressive phenotypes including metastasis.
The phase III ARAMIS study shows that the androgen-receptor antagonist darolutamide delays metastasis in men with castration-resistant prostate cancer by a median of 22 months compared with a placebo.
It was found that there was no significant difference between androgen receptor expression and susceptibility, pathological type, metastatic status, metastatic type (lymph or distant metastasis) and cancer-specific survival of renal cell carcinoma (P > 0.05).
Some studies have shown that the activation of other signalling pathways in CRPC cells replaces the function of the androgen receptor, as well as promotes cell metastasis and progression.
The inevitable progression of advanced prostate cancer to castration resistance, and ultimately to lethal metastatic disease, depends on primary or acquired resistance to conventional androgen deprivation therapy (ADT) and accumulated resistance strategies to evade androgen receptor (AR) suppression.
Since therapies that target the AR are the mainstay treatment for men with metastatic disease, it is essential to understand the molecular mechanisms underlying oncogenic AR signaling in the prostate.
Patients with metastasis prostate cancer underwent androgen deprivation therapy (ADT) in the considering of the leading role of androgen receptor pathway.
Among the six ECM genes, SPP1 was identified as the key hub signature for PCa metastasis and drug resistance development; we found that both protein and mRNA expression levels of SPP1 were remarkably up-regulated in mCRPC compared with HSPC in organoid models and could regulate the androgen receptor signaling pathway.
SIGNIFICANCE OF THE STUDY: This review is targeting DUB proteins which are responsible for PCa induction, proliferation, and metastasis by highlighting their signalling pathway so that the readers can get information about other mechanisms for PCa besides androgen receptor pathway and helps to find other oncogenic DUBs involving in these signalling pathways.
Coexpression analyses showed an increase of the double-positive (AR<sup>+</sup> /ARv7<sup>+</sup> ) population in metastases compared to benign, and an increase of the double-negative population in PRCA samples compared to benign.
While HOXB13 regulates Androgen Receptor (AR) functions in a context dependent manner, its critical effectors in prostate cancer (PC) metastasis remain largely unknown.