Abstract
Prostate cancer is the second most common male malignancy, with a highly variable clinical presentation and outcome. Therefore, diagnosis, prognostication, and management remain a challenge, as available clinical, imaging, and pathological parameters provide limited risk assessment. Thus, many biomarkers are under study to fill this critical gap, some of them based on epigenetic aberrations that might be detected in liquid biopsies. Herein, we provide a critical review of published data on the usefulness of DNA methylation and circulating tumor cells in diagnosis and treatment decisions in cases of prostate cancer, underlining key aspects and discussing the importance of these advances to the improvement of the management of prostate cancer patients. Using minimally invasive blood tests, the detection of highly specific biomarkers might be crucial for making therapeutic decisions, determining response to specific treatments, and allowing early diagnosis.
Highlights
A multicenter study enrolling 118 men demonstrated that patients with at poorrisk of metastatic CRPC (mCRPC) and whose circulating tumor cells (CTCs)’ androgen receptor splice variant 7 (AR-V7) status was positive did not benefit from abiraterone or enzalutamide therapy but could still benefit from docetaxel or cabazitaxel treatment [83]
Sharp et al showed that patients with CTCs not detectable by the AdnaTest method often demonstrate the isolation of CTCs on the CellSearch platform and express AR-V7 protein that matches the tumor tissue [120], highlighting the importance of the detection method and the gene expression concordance between tumor tissue and CTCs
The detection of biomarkers in CTCs might be advantageous for therapeutic decisions, especially if CTCs are indicative of response to specific treatments and could aid in early diagnosis
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. 10–20% of patients with metastasized PCa develop castration-resistant disease (CRPC) within 5 years, with a median survival of only 14 months [8,9,10]. Next-generation hormonal therapies, such as the CYP17A1 inhibitor abiraterone, which impairs the androgen synthesis pathway, or the AR antagonist enzalutamide, are options for metastatic CRPC (mCRPC); acquired resistance usually arises within 2 years [16,17], and none of these treatments are curative [10], reinforcing the urgent need for new therapeutic approaches. It is imperative to develop biomarkers that might be assessed using non- or minimally invasive techniques, enabling the real-time follow-up of minimal residual disease, recurrence, and metastization, as well as therapy-resistant clonal selection within tumor cell populations [21].
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