Recent advances on the progressive mechanism and therapy in castration-resistant prostate cancer

Abstract

BackgroundAlthough there have been great advances in mechanisms and therapeutic methods of prostate cancer, the mortality rate of prostate cancer remains high. The castration-resistant prostate cancer (CRPC), which develops from hormone-sensitive prostate cancer, foreshadows a more dismal outcome. Concomitant with the researches in the mechanism of CRPC and therapy for CRPC, more and more landmark progress has been made in recent years.MethodsA number of clinical and experimental studies were reviewed to indicate the novel advancement in the progressive mechanism and therapy of CRPC.ResultsThe androgen receptor (AR) is still a vital driver in the progression of CRPC, while other multiple mechanisms also contribute to this progression, such as tumor immunity, cancer stem cells, epithelial–mesenchymal transition and DNA repair disorder. In terms of the therapeutic methods of CRPC, chemotherapy with drugs, such as docetaxel, has been the first-line therapy for CRPC for many years. Besides, newer agents, which target some of the above mechanisms, show additional overall survival benefits for CRPC patients. These therapies include drugs targeting the androgen axis pathway (androgen synthesis, androgen receptor splice variants, coactivators of AR and so on), PI3K-AKT pathway, WNT pathway, DNA repair, rearrangement of ETS gene, novel chemotherapy and immunotherapy, bone metastasis therapy and so on. Understanding these novel findings on the mechanisms of CRPC and the latest potential CRPC therapies will direct us for further exploration of CRPC.ConclusionThrough comprehensive consideration, the predominant mechanism of CRPC might be the AR signal axis concomitant with tumor microenvironment, stress, immunity, tumor microenvironment and so on. For CRPC therapy, targeting the AR axis pathway and chemotherapy are the first-line treatments at present. However, with the advancements in CRPC therapy made by the researchers, other novel potential methods will occupy more and more important position in the treatment of CRPC, especially the therapies targeting the tumor microenviroment, tumor immunity and DNA repair and so on.

Fli-1 Activation through Targeted Promoter Activity Regulation Using a Novel 3’, 5’-diprenylated Chalcone Inhibits Growth and Metastasis of Prostate Cancer Cells

“…For treating highly metastatic prostate cancers, therapeutic strategies still mainly rely on targeting the androgen receptor (AR) axis pathway by various means such as inhibiting the synthesis of androgens; targeting the ligand binding region, DNA binding domain, or n-terminal structural domain (NTD) of AR; and using AR antagonists. However, although this approach may extend the survival time to a certain extent, drug resistance will finally lead to the failure of AR signal axis targeting therapy [42]. Therefore, developing new therapeutic targets and corresponding targeted drugs is an urgent requirement.…”

The Prognostic Value and Mechanisms of TMEM16A in Human Cancer

“…PC originated from glandular epithelial cells and is one of the most common malignancies in males ( Wang K. et al, 2018 ). PC is estimated to be the second leading cause of death in male malignancies ( Dijkstra et al, 2014 ).…”

Dopamine receptor antagonists induce differentiation of PC‐3 human prostate cancer cell‐derived cancer stem cell‐like cells

“…Although the 5‐year survival rate of prostate cancer is 99% in the USA, prostate cancer is the second leading cause of male cancer‐related death due to its high incident rate . As in the case of many different types of cancer, recurred or metastasized prostate cancer is also highly resistant to anticancer drugs, for which several mechanisms have been proposed, including androgen receptor (AR) gain‐of‐function, loss of tumor suppressor genes, alteration in growth factor signaling, and presence of cancer stem cells (CSCs). In the recent few decades, significant progress has been made in understanding the role of CSCs in the development of cancer resistance to anticancer drugs or radiotherapy .…”