Novel strategies in the treatment of castration-resistant prostate cancer (Review)

Abstract

Abstract. Prostate cancer is the most common cancer in men in Europe and the United States, and the third leading cause of death from cancer in Europe. Survival of prostate cancer cells is dependent on the activation of androgen receptors (AR), that are overexpressed in this tumor. Furthermore, ~90% of prostate cancer patients that respond to first-line androgen deprivation therapy (ADT) undergo rapid progression. This condition is defined as castration-resistant prostate cancer (CRPC). Docetaxelbased regimens significantly improve overall survival (OS) in patients with CRPC and represent the only treatment strategy approved by the Food and Drug Administration (FDA). Recently, abiraterone (second hormonal therapy) and cabazitaxel (new taxane) have been shown to improve survival in patients with CRPC who progressed following docetaxel-based chemotherapy. Vaccine therapy has also been demonstrated to improve OS in patients with asymptomatic or minimally symptomatic metastatic CRPC. Additional therapeutic targets have been analyzed in prostate cancer, including apoptosis, angiogenic receptors, vitamin D and Src pathways. Several phase II studies are ongoing. The high frequency of prostate cancer-related metastatic bone disease has led to consider this pathway as a therapeutic target. To this end, several bone-targeted agents have been investigated, most notably zoledronic acid, which is highly effective at stabilizing the bone and preventing skeletal complications. More recently, a nuclear factor-β ligand (RANKL) inhibitor, denosumab, has been developed for the treatment of bone metastases.

Piperine, a Bioactive Component of Pepper Spice Exerts Therapeutic Effects on Androgen Dependent and Androgen Independent Prostate Cancer Cells

“…The early-stage prostate cancer depends on androgens for growth and survival, and androgen ablation therapy causes them to regress [22]. Cancers that are not cured by hormonal therapy eventually become androgen independent, rendering anti-androgen therapy ineffective [22],[23]. Furthermore, our investigations also revealed that piperine is an inducer of apoptosis in prostate cancer cells as evident from Annexin-V immunofluorescence staining studies.…”

Intra-tumoral delivery of functional ID4 protein via PCL/maltodextrin nano-particle inhibits prostate cancer growth

“…Thus understanding the molecular basis of resistance and discovering therapeutic strategies/agents that can overcome the resistant pathways is urgently needed. In an effort to increase survival, combination DTX therapies that target androgen receptor pathway, angiogenesis, apoptosis and growth factors are currently under clinical trials [37]. The L(-)ID4 tumors also appeared at least partially resistant to DTX, analogous to DTX resistant, androgen insensitive C81 cells [38].…”

A novel approach to identify driver genes involved in androgen-independent prostate cancer

“…PCa is initially androgen-dependent, making androgen deprivation therapy the first line of defense in combating the disease [11]. Though this treatment initially reduces tumor size, patients eventually develop AIPC, which is resistant to this primary form of therapy and is ultimately lethal [11-13]. Thus, determining the mechanisms that contribute to AIPC is critical to develop novel therapies for this advanced form of PCa.…”