Dissecting major signaling pathways in prostate cancer development and progression: Mechanisms and novel therapeutic targets

Abstract

Prostate cancer (PCa) is the most frequently diagnosed non-cutaneous malignancy and leading cause of cancer mortality in men. At the initial stages, prostate cancer is dependent upon androgens for their growth and hence effectively combated by androgen deprivation therapy (ADT). However, most patients eventually recur with an androgen deprivation-resistant phenotype, referred to as castration-resistant prostate cancer (CRPC), a more aggressive form for which there is no effective therapy presently available. The current review is an attempt to cover and establish an understanding of some major signaling pathways implicated in prostate cancer development and castration-resistance, besides addressing therapeutic strategies that targets the key signaling mechanisms.

Keywords: Androgen; Castration resistant prostate cancer; Prostate cancer; Signaling pathways.

Fig. 1.

Chief signaling pathways involved in PCa development and progression. (1) Wnt/β-catenin signaling, (2) AR signaling, (3) NF-κB signaling, (4) JAK/STAT signaling and (5) receptor tyrosine kinase signaling. Abbreviations: AKT, akt serine/threonine kinase; AR, androgen receptor; ARE, androgen responsive elements; β-Cat, beta-catenin; DHT, dihydrotestosterone; GF, growth factor; Fz, Frizzled receptor; IκB, inhibitor of kappa B; ILs, interleukins; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa B; PI3K, phosphoinositide-3-kinase; Ras, rat sarcoma protein; RTK, receptor tyrosine kinase; STAT, signal transducers and activators of transcription; TCF/LEF-1, t-cell specific transcription factor/lymphoid enhancer-binding factor; Wnt, wnt ligands.

Fig. 2.

Chemical Structures of some of the approved/in development Prostate Cancer Drugs.