Summary Background:  Castration‐resistant prostate cancer (CRPC) is an advanced form of prostate cancer associated with poor survival rates. However, characterisation of the disease epidemiology is hampered by use of varying terminology, definition and disease management. The aim of this review was to conduct a systematic review to provide greater clarity on the sum of the available epidemiologic evidence and to guide future research into the disease prevalence, progression, characteristics and outcome. Methods:  Systematic searches of PubMed and Embase were performed in March 2010 to identify relevant observational studies relating to the epidemiology, progression and outcomes of CRPC. Further studies were identified for inclusion in our review through manual searches of the authors’ bibliographical databases and the reference lists of the included articles. Results:  We identified 12 articles (10 full papers and 2 abstracts) reporting studies that included a total of 71,179 patients observed for up to 12 years for evaluation in our review. Five studies looked at the prevalence of CRPC in patients with prostate cancer. Together, the data indicate that 10–20% of prostate cancer patients develop CRPC within approximately 5 years of follow‐up. Two studies reported the prevalence of bone metastases present at diagnosis of CRPC. Together, ≥ 84% were shown to have metastases at diagnosis. Of those patients with no metastases present at diagnosis of CRPC, 33% could expect to develop them within 2 years. The median survival of patients with CRPC was reported in five studies, with values varying from 9 to 30 months. A pooled, sample‐weighted survival estimate calculated from the survival data included in this review is 14 months. Very few studies that met our inclusion criteria evaluated treatment patterns in CRPC. One study reported that only 37% of patients with CRPC received chemotherapy, with the remainder receiving only steroids and supportive care. The most common palliative therapies administered to patients with skeletal symptoms were radiotherapy, radionuclide therapy, bisphosphonates and opioids. Conclusions:  This review highlights the poor prognosis of patients with CRPC, and demonstrates a survival of 9–13 months in those patients with metastatic CRPC. Furthermore, progression to CRPC is associated with deterioration in quality of life, and few therapeutic options are currently available to patients with CRPC. However, epidemiologic study of these patients is hampered by differing terminology, definitions and treatment paradigms. Our review highlights the need for further well‐designed, epidemiological studies of CRPC, using standardised definitions and methods.

The epibranchial placodes are cranial, ectodermal thickenings that give rise to sensory neurons of the peripheral nervous system. Despite their importance in the developing animal, the signals responsible for their induction remain unknown. Using the placodal marker, sox3, we have shown that the same Fgf signaling required for otic vesicle development is required for the development of the epibranchial placodes. Loss of both Fgf3 and Fgf8 is sufficient to block placode development. We further show that epibranchial sox3 expression is unaffected in mutants in which no otic placode forms, where dlx3b and dlx4b are knocked down, or deleted along with sox9a. However, the forkhead factor, Foxi1, is required for both otic and epibranchial placode development. Thus, both the otic and epibranchial placodes form in a common region of ectoderm under the influence of Fgfs, but these two structures subsequently develop independently. Although previous studies have investigated the signals that trigger neurogenesis from the epibranchial placodes, this represents the first demonstration of the signaling events that underlie the formation of the placodes themselves, and therefore, the process that determines which ectodermal cells will adopt a neural fate.

Little is known of the first transcriptional events that regulate neural fate in response to extracellular signals such as Bmps and Fgfs. Sox3 is one of the earliest transcription factors to be expressed in the developing CNS and has been shown to be regulated by these signalling pathways. We have used both gain- and loss-of-function experiments in zebrafish to elucidate the role of Sox3 in determining neural fate. Ectopic Sox3 caused induction of neural tissue from a very early stage of cell specification in the ectoderm and this effect was maintained such that large domains of additional CNS were apparent, including almost complete duplications of the CNS. Knock-down of Sox3 using morpholinos resulted in a reduction in the size of the CNS, ears and eyes and subsequent inhibition of some aspects of neurogenesis. Our data also suggest that the pro-neural effects of Sox3 can compensate for inhibition of Fgf signalling in inducing neural tissue but it is not sufficient to maintain neural fate, suggesting the presence of Sox3-independent roles of Fgf at later stages.