Transforming growth factor (TGF)-beta expression and activation mechanisms as potential targets for anti-tumor therapy and tumor imaging

Cancer remains one of the leading causes of death in the developed countries and cancer mortality is expected to rise globally. Despite encouraging developments regarding targeted drugs, the most prevalent cancer mortality remains metastatic disease. Therefore, drugs that target cancer progression, invasion and metastasis are clearly needed. One of the most interesting targets in this setting is transforming growth factor beta (TGF-beta). TGF-beta can promote tumor growth, invasion and metastasis. However, TGF-beta also has a physiological, opposing role: maintaining tissue homeostasis and suppression of tumor progression. The window of effective TGF-beta targeting is therefore evidently small, which poses a clear challenge in selecting patients at the right time. Despite this complexity, several TGF-beta inhibitors are currently in clinical development, modulating TGF-beta production, activation or signaling. Still, specificity and long term toxicity remain unclear, emphasizing the importance of careful monitoring of clinical trials.

Development and application of these drugs in the clinic require adequate insight and evaluation methods for the role of TGF-beta during tumor invasion and metastasis. In this review, presently available methods for clinical evaluation will be discussed, such as an ex vivo stimulation assay, TGF-beta response signature and molecular imaging techniques. Future clinical trials incorporating the validation of these evaluation methods will show which method will be most predictive and suitable for clinical application. (C) 2012 Elsevier Inc. All rights reserved.