The power and promise of “rewiring” the mitogen-activated protein kinase network in prostate cancer therapeutics

• Published in: Molecular cancer therapeutics 2007-03, Vol.6 (3), p.811-819
• Main Authors: Papatsoris, Athanasios G, Karamouzis, Michalis V, Papavassiliou, Athanasios G
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Enzyme Inhibitors - therapeutic use; Humans; Male; MAPK; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - enzymology; Raf; Ras; Signal transduction; Signal Transduction - drug effects
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.MCT-06-0610

Prostate cancer is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. Initially, tumor growth is androgen dependent and thus responsive to pharmacologic androgen deprivation, but there is a high rate of treatment failure because the disease evolves in an androgen-independent state. Growing evidence suggests that the Ras/mitogen-activated protein kinase (MAPK) signaling cascade represents a pivotal molecular circuitry participating directly or indirectly in prostate cancer evolution. The crucial role of the protein elements comprising this complex signal transduction network makes them potential targets for pharmacologic interference. Here, we will delineate the current knowledge regarding the involvement of the Ras/MAPK pathway in prostate carcinogenesis, spotlight ongoing research concerning the development of novel targeted agents such as the Ras/MAPK inhibitors in prostate cancer, and discuss the future perspectives of their therapeutic efficacy. [Mol Cancer Ther 2007;6(3):811–9]