Radiotherapy and inhibition of the EGF family as treatment strategies for prostate cancer: combining theragnostics with theragates

Prostate cancer is one of the most common solid tumors affecting men. Localized stages can be cured, however, once disseminated to distant organs the median survival drops below 12 months. The challenge for the future consists of unifying gained insights of cellular signal dysfunctioning (‘‘theragates’’) with the knowledge of disease detection (‘‘theragnostics’’) in personalized therapy. In solid malignancies, multiple signal transduction molecules are often deregulated simultaneously, within the same tumor. A multi-targeted approach may possibly improve efficacy, but will also increase toxicity, thus, potentially limiting the use of various combinations. On the other hand, well-established treatment modalities in prostate cancer, such as radiotherapy with its known efficacy and limited toxicity, may be an attractive combination partner for protein kinase inhibitors. Deregulation of the epidermal growth factor receptor (EGFR) signal transduction pathway is observed in a variety of solid tumors, including prostate cancer. Furthermore, one important DNA repair mechanism is dependent on EGFR nuclear translocation, thus, providing a rationale for combining radiotherapy with EGFR inhibitors. This article reviews current knowledge regarding this combination paradigm, revealing an intriguing therapy option to be explored for patients with advanced prostate cancer.