Signal Transduction Targets in Prostate Cancer

Hari   K.   Koul; Lakshmipathi      Khandrika

Abstract

According to the American Cancer Society, Prostate cancer (PCa) is the second leading cause of cancer deaths in men. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is no cure once the disease has spread beyond the prostate. Androgens are the primary growth factors used by prostate cancer cells initially, and androgen deprivation remains the only treatment for men with clinically advanced stage disease; however, prostate cancer cells eventually progress to androgen independence, and androgen refractory prostate cancer is ultimately responsible for the death of PCa patients. There is at present no effective treatment for hormone-independent PCa. Normal prostate epithelial cells as well as early-stage-prostate cancer cells depend on androgens for growth and survival. However, several molecular mechanisms like mutations to the androgen receptor (AR), cross-talk between the AR and other molecular pathways can lead to an independence from androgens for growth. These casual molecular genetic changes lead to an epigenetic mechanism where a feed-back autocrine loop between membrane receptors and associated ligands serves as an essential component of growth, proliferation and metastasis of prostate cancer at an advanced and androgen-independent stage. Peptide growth factors and cytokines are known to exert their effects by a complex array of mechanisms primarily mediated by signal transduction pathways. Thus, we rationalized that inhibiting these epigenetic events could serve as an approach in treatment of advanced prostate cancer. In this article we have reviewed all the relevant literature that describe signal transduction pathways in prostate gland under normal and malignant conditions. We will also try to identify possible signal transduction targets for the treatment of prostate cancer.

Keywords: MAP kinase, LNCaP cells, Proliferation, Protein Signaling, ERK5 Activation