Molecular Pathways in the Progression of Hormone-Independent and Metastatic Prostate Cancer

B.      Wegiel; S.      Evans; R.      Hellsten; L.E.      Otterbein; A.      Bjartell; J.L.      Persson

Abstract

Once prostate cancer becomes castration resistant, cancer cells may rapidly gain the ability to invade and to metastasize to lymph nodes and distant organs. The progression through hormone-dependent to hormone-independent/ castration-resistant and metastatic PCa is poorly understood. In this review paper, we provide an overview on the cellular and molecular mechanisms underlying the process of tumor cell invasion and metastasis in prostate cancer. We specifically presented the most recent findings on the role of multiple cellular signaling pathways including androgen receptor (AR), mitogen-activated protein kinases (MAPK), Akt, transforming growth factor β (TGFβ), interleukin-6 (IL- 6) and vascular endothelial growth factor (VEGF) in the development of hormone-independent/castration-resistant prostate cancer. In addition, we also discussed the recent findings on signatures of gene expression during prostate cancer progression. Our overviews on the novel findings will help to gain better understanding of the complexity of molecular mechanisms that may play an essential role for the development of castration-resistant and metastatic prostate cancer. It will also shed light on the identifying specific targets and design effective therapeutic drug candidates.

Keywords: Prostate cancer, androgen receptor, molecular pathways, castration resistance

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