title: Transforming growth factor (TGF)-β expression and activation mechanisms as potential targets for anti-tumor therapy and tumor imaging.
abstract: 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 β (TGF-β). TGF-β can promote tumor growth, invasion and metastasis. However, TGF-β also has a physiological, opposing role: maintaining tissue homeostasis and suppression of tumor progression. The window of effective TGF-β targeting is therefore evidently small, which poses a clear challenge in selecting patients at the right time. Despite this complexity, several TGF-β inhibitors are currently in clinical development, modulating TGF-β 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-β 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-β 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.
authors.affiliation: Department of Medical Oncology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Marlous
authors.initials: M
authors.lastname: Arjaans
authors.forename: Thijs H
authors.initials: TH
authors.lastname: Oude Munnink
authors.forename: Hetty
authors.initials: H
authors.lastname: Timmer-Bosscha
authors.forename: Michael
authors.initials: M
authors.lastname: Reiss
authors.forename: Annemiek M E
authors.initials: AM
authors.lastname: Walenkamp
authors.forename: Marjolijn N
authors.initials: MN
authors.lastname: Lub-de Hooge
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: Carolina P
authors.initials: CP
authors.lastname: Schröder
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta