title: New agents for prostate cancer.
abstract: The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand. Emerging androgen pathway inhibitors include androgen synthesis inhibitors (TAK700), androgen receptor inhibitors (ARN-509, ODM-201), AR DNA binding domain inhibitors (EPI-001), selective AR downregulators or SARDs (AZD-3514), and agents that inhibit both androgen synthesis and receptor binding (TOK-001/galeterone). Promising immunotherapeutic agents include poxvirus vaccines and CTLA-4 inhibitor (ipilimumab). Biologic agents targeting the molecular drivers of disease are also being investigated as single agents, including cabozantinib (Met and VEGFR2 inhibitor) and tasquinimod (angiogenesis and immune modulatory agent). Despite the disappointing results seen from studies evaluating docetaxel in combination with other agents, including GVAX, anti-angiogentic agents (bevacizumab, aflibercept, lenalinomide), a SRC kinase inhibitor (dasatinib), endothelin receptor antagonists (atrasentan, zibotentan), and high-dose calcitriol (DN-101), the results from the trial evaluating docetaxel in combination with the clusterin antagonist, custirsen, are eagerly awaited. New therapeutic hurdles consist of discovering new targets, understanding resistance mechanisms, the optimal sequencing and combinations of available agents, as well as biomarkers predictive for benefit. Novel agents targeting bone metastases are being developed following the success of zoledronic acid and denosumab. Finally, all of these modalities do not appear curative, suggesting that clinical trial enrollment and a better understanding of biology remain of paramount importance.
authors.affiliation: Division of Medical Oncology, University of Utah Huntsman Cancer Institute, Salt Lake City, USA.
authors.forename: N
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: Department of Endocrinology and Medical Oncology, Genitourinary Cancer Section, University Federico II, Napoli, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Di Lorenzo
authors.affiliation: Department of Medicine, Division of Hematology Oncology, University of Alabama at Birmingham (UAB) Comprehensive Cancer Center, Birmingham.
authors.forename: G
authors.initials: G
authors.lastname: Sonpavde
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, USA and; University Hospital del Mar-IMIM, Barcelona, Spain. Electronic address: joaquim.bellmunt@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Bellmunt
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use; D059002:Androgen Receptor Antagonists / Q000627:therapeutic use; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D055808:Drug Discovery; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D065088:Steroid Synthesis Inhibitors / Q000627:therapeutic use
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D065128:Endothelin Receptor Antagonists; D065088:Steroid Synthesis Inhibitors
keywords: novel agents; prostate cancer