Targeted therapeutic approaches for hormone-refractory prostate cancer.

Abstract

Prostate cancer is one of the leading causes of cancer related death in men, and remains incurable in the metastatic setting. Despite the initial response to androgen deprivation, the disease gradually progresses to a hormone-refractory state due to cumulative genetic alterations in tumour cells or the microenvironment. Docetaxel represents the first chemotherapeutic agent with a small survival benefit for metastatic hormone-refractory prostate cancer (HRPC). In an attempt to improve survival benefit, several novel drugs targeting specific pathways involved in cell signaling, proliferation, angiogenesis, apoptosis and immune modulation are currently under investigation either as single agents or in combination with cytotoxic drugs. Clinical trials evaluate the inhibition of prostate cancer cells growth by targeting the nuclear receptor of vitamin D alongside cytotoxic therapy. Angiogenesis inhibitors as well as epidermal growth factor receptor blockage are also under clinical investigation in several combinations. Immunomodulatory agents and autologous dendritic cells or allogenic whole cell vaccines have progressed up to phase III trials. New drugs targeting bone microenvironment or apoptotic and proliferation pathways may enhance antitumour activity of chemotherapy in HRCP. Given the complexity of mechanisms underlying prostate cancer progression, future therapeutic strategies should rely on multidisciplinary approaches, thus exploiting newer molecular targets in concert with immunotherapy and cytotoxic chemotherapy. Here, we review the latest clinical evidence regarding the use of novel agents in HRPC.

• Authors: Flora Stavridi, Eleni M Karapanagiotou, Kostas N Syrigos
• Journal: Cancer treatment reviews (Cancer Treat Rev) Vol. 36 Issue 2 Pg. 122-30 (Apr 2010) ISSN: 1532-1967 [Electronic] Netherlands
• PMID: 20106600 (Publication Type: Journal Article, Review)
• Copyright: Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Drug Resistance, Neoplasm (drug effects)
• Drug Therapy, Combination
• Humans
• Immunotherapy (methods)
• Male
• Prognosis
• Prostatic Neoplasms (drug therapy)