Molecular pathways in the progression of hormone-independent and metastatic prostate cancer.
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 present 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 b (TGFb interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in the development of hormone-independent/castration-resistant prostate cancer. In addition, we also discuss 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 in the development of castration-resistant and metastatic prostate cancer. It will also shed light on the identification of specific targets and the design of effective therapeutic drug candidates.
Wegiel
B
B
Department of Surgery, Transplant Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Evans
S
S
Hellsten
R
R
Otterbein
L E
LE
Bjartell
A
A
Persson
J L
JL
D000728:Androgens / Q000502:physiology*; D018450:Disease Progression; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
D000728:Androgens