Abstract
Prostate cancer (PCa) is the second most common killer among men in Western countries. Targeting androgen receptor (AR) signaling by androgen deprivation therapy (ADT) is the current therapeutic regime for patients newly diagnosed with metastatic PCa. However, most patients relapse and become resistant to ADT, leading to metastatic castration-resistant PCa (CRPC) and eventually death. Several proposed mechanisms have been proposed for CRPC; however, the exact mechanism through which CRPC develops is still unclear. One possible pathway is that the AR remains active in CRPC cases. Therefore, understanding AR signaling networks as primary PCa changes into metastatic CRPC is key to developing future biomarkers and therapeutic strategies for PCa and CRPC. In the current review, we focused on three novel biomarkers (ZBTB46, SPDEF, and ETV6) that were demonstrated to play critical roles in CRPC progression, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) drug resistance, and the epithelial-to-mesenchymal transition (EMT) for patients treated with ADT or AR inhibition. In addition, we summarize how these potential biomarkers can be used in the clinic for diagnosis and as therapeutic targets of PCa.
Highlights
Prostate cancer (PCa) is the most common cancer expected to occur in men with an estimated 164,690 new cases annually in the US, and it is the second most common cause of cancer deaths in men after lung cancer [1]
The first biomarker used for PCa screening was prostatic acid phosphatase (PAP) [3], the use of which was limited in the clinic once screening with the prostate-specific antigen (PSA) was initiated in 1970 [4]
Chen et al showed that in androgen deprivation therapy (ADT)-treated PCa, zinc finger and BTB domain-containing protein 46 (ZBTB46) levels were enhanced by loss of the expression of the SAM pointed domain-containing ETS transcriptional factor (SPDEF), which is believed to act as a tumor suppressor gene and to be regulated by androgen receptor (AR) signaling [118]
Summary
Prostate cancer (PCa) is the most common cancer expected to occur in men with an estimated 164,690 new cases annually in the US, and it is the second most common cause of cancer deaths in men after lung cancer [1]. Several guidelines were developed to enhance PCa screening in place of the PSA test, decrease unnecessary biopsies, and increase the specificity for cancer detection.
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