New developments in castrate‐resistant prostate cancer

Abstract

Castrate‐resistant prostate cancer (CRPC) occurs when disease progresses in the presence of castrate levels of androgens and remains sensitive to further hormonal manipulation. For many years the treatment of CRPC was limited to the use of docetaxel for metastatic disease. However, this has recently changed with the approval of several new agents. Sipuleucel‐T, an immunotherapeutic vaccine, is now available in the US for patients with non‐metastatic CRPC and abiraterone, an oral enzyme inhibitor of androgen biosynthesis, as well as cabazitaxel, a cytotoxic chemotherapeutic, have been approved for the treatment of metastatic CRPC. Also, denosumab, a subcutaneous antibody, is now an option for the treatment of patients with CRPC with bone metastases, in addition to zoledronic acid, an intravenous bisphosphonate. Further treatment advances for metastatic CRPC therapeutics are in late stage phase III development. These include therapies affecting the androgen receptor (MDV3100) as well as additional immune‐based therapeutics, PROSTVAC and ipilimumab. A broad range of agents is also emerging under the term targeted therapies. The endothelin‐A receptor antagonist zibotentan, the tyrosine kinase inhibitors dasatinib, sorafenib and cabozantinib, the anti‐angiogenic agent aflibercept, and the clusterin inhibitor custirsen, are all currently being tested for efficacy in metastatic CRPC. The mechanism of action of these and other promising agents are discussed alongside current therapeutic options and their potential place in the treatment landscape for CRPC is considered.

Hypoxia regulates ANXA1 expression to support prostate cancer cell invasion and aggressiveness

“…36 The process by which PCa cells become hormone-resistant is unidentified, but it has been proposed that hormone depletion could result in a selective advantage to androgen-independent cells, which grow, repopulate the tumor and eventually migrate away from the original site to give rise to metastasis. 37 The evolution from hormone-dependent to hormone-independent PCa is supposed to be an effect of genetic alterations, 38 however numerous evidences are accumulating about the role of tumor microenvironment on the outset of a metastatic disease. 39 Hypoxia is an essential feature of the microenvironment of several solid tumors including those of PCa.…”

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

“…24 Nilotinib is a TKI that targets Bcr-Abl as well as other kinases, including PDGFR-α, KIT, discoidin domain receptor, and colony-stimulating factor receptor-1. 25 Nilotinib is currently approved by the FDA for the treatment of imatinib-resistant chronic myeloid leukemia.…”

LG308, a Novel Synthetic Compound with Antimicrotubule Activity in Prostate Cancer Cells, Exerts Effective Antitumor Activity

“…In the past few years, great strides have been made for identifying effective and new therapies for PCa (Shore et al, 2012), but most PCa cases ultimately relapsed and progressed to intractable castration-resistant PCa (CRPC) (Xu and Zhang, 2014). Traditional chemotherapy was applied clinically for the treatment of CRPC.…”