Ciência e terapia do câncer

Are Genetic Alterations an Important Factor in the Development and Progression of Prostate Cancer?

Abstract

Adithan Ganesh

Prostate cancer (PC) is the second most common cancer in the UK and the most common cancer in males. The aetiology of PC is poorly understood and the molecular events that underpin the disease are yet to be elucidated. A number of studies have been aimed at the genetic determinants that contribute to the development and progression of PC and this review focused on the TMPRSS2-ERG, EZH2 and PTEN genes. The TMPRSS2-ERG fusion gene has been detected in 50% of PC cases and its specificity to PC makes it hugely relevant in PC development. ERG overexpression is sufficient to induce cell invasive programmes in vitro and metastasis in vivo. While its role as a prognostic biomarker is controversial, it is still a promising therapeutic target. The EZH2 gene has also been implicated in a number of cancers but its extensive upregulation in PC makes it particularly culpable. Studies in vitro and in vivo have demonstrated its ability to contribute to PC progression via epigenetic silencing of key tumour suppressor genes. Lastly, the PTEN gene is involved in the development and progression of PC via its interaction with the PI3K/mTOR pathway. Variations in PTEN dose are able to recapitulate the different stages of PC in vivo and are associated with poor patient prognosis. The studies highlighted in this review do support genetic alterations as being an important factor in the development and progression of PC, however other risk factors must be considered alongside the genetics of the disease.