Dissecting prostate carcinogenesis through ETS gene rearrangement studies: implications for anticancer drug development.
The discovery of ETS gene fusions as common events in prostate cancer represents a paradigmatic shift in the significance attributed to chromosomal translocations as a key mechanistic player in carcinogenesis. However, these chromosomal fusion events are poorly understood, as their functional significance and therapeutic potential remain unclear. Nonetheless, they have generally been used as novel molecular handles to sub-categorise the broad diversity of prostate cancers mainly via the use of fluorescence in-situ hybridisation-based "break-apart assays". Thus, the potential roles of these ETS gene fusion events are being actively explored and are discussed in this review within the context of the existing scientific and clinical climates. Examples include their possible utilities as screening tools, markers for risk stratification and predictors of responses to therapies (in particular hormonal manipulation), biomarkers to guide early phase clinical trials, as well as therapeutic targets. Work is ongoing to address the many questions surrounding these pursuits in a very rapidly evolving area of research, and it is believed that an improved understanding of the biology underpinning these genetic events is vital in order to optimise their use in anticancer drug development.
Attard
G
G
The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
Ang
J E
JE
Olmos
D
D
de Bono
J S
JS
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D050939:Gene Fusion; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; C529660:TMPRSS2-ETS fusion protein, human