Proefschrift

CHAPTER 1. INTRODUCTION cancer has been a part of the entire human history as well. The Edwin Smith Papyrus, written approximately 3500 years ago, contains the first documented description of cancer. Amazingly, prostate cancer itself has been confirmed in a 2700 year old Scythian king and a 2250 year old Ptolemaic mummy (Figure 1.1) (Schultz et al., 2007; Prates et al., 2011). Both of these men were estimated to have lived more than 40 years, which is well beyond the estimated average life span at the time of 28–36 years (Angel, 1969). Figure 1.1: Panels a-c: Lesions in right humerus of the 2,700 year old Scythian king from Arzhan. (a) Macroscopic view. The shaft, whose surface is characterized by secondarily built bone plates, is clearly thickened in its proximal part due to tumorous growth. (b) Scanning electron microscopic image. Smooth and porous bony plates on the external surface of the shaft of right humerus which are a characteristic feature of tumor periostosis. (c) Cross section through shaft of right humerus. Bony plates on the external surface of shaft. The compact bone substance is severely damaged by resorption holes due to osteoclastic activity. Microphotograph of thin ground section (thickness 50 μm) viewed in polarized light using a hilfsobject red 1st order (quartz) as compensator. Scale of bar 200 μm. Panel (d) M1, the Ptolemaic wrapped human mummy from the MNA Egyptian Collection. Panel (e) MDCT MPR (sagittal) of the lumbar spine, showing sclerotic vertebral bone lesions. Reprinted from Schultz et al. (2007) with permission from John Wiley and Sons and reprinted from Prates et al. (2011) with permission from Elsevier. The first report of an abnormal prostate gland consistent with the modern description of primary prostate cancer came in 1817 by George Langstaff (Langstaff, 1817). While the first documented case of prostate cancer was recorded in 1853 by John Adams, it wasn’t until the 1940’s that Charles Huggins introduced the first treatment for prostate cancer using oral oestrogens as a means of chemical castration (Adams, 1853). Interestingly, this systemic treatment protocol, as opposed to surgery or local radiation techniques, was the first effective systemic therapy for any cancer and brought Huggins the Nobel Prize in 1966 (Denmeade and Isaacs, 2002). This resulted in a flurry of research, discovery, and clinical 4