Jak2/Stat5a/b Signaling Axis and Novel Therapeutic Strategies in Prostate Cancer

Prostate cancer (PCa) is the third leading cause of cancer death in the US. It is a heterogeneous disease with clinical course ranging from indolent disease to rapidly progressing, often fatal disease. Complex molecular mechanisms lead to development of metastatic castrate-resistant prostate cancer (CRPC) for which no curative therapies exist. There is an urgent need to develop rational biomarkers and therapeutic targets that will help expedite discovery of curative therapies. This chapter describes the treatment options for localized and metastatic PCa and provides an in-depth review of the Jak2/Stat5a/b signaling pathway in PCa, which is critical in prostate cancer progression, development of castrate-resistance and metastases. Target validation of Jak2/Stat5a/b pathway is discussed in detail, including the role of pharmacological inhibitors of Jak2 and Stat5a/b, providing a strong rationale for targeting this pathway to improve outcomes in PCa. Furthermore, the prognostic and predictive significance of Stat5a/b in providing personalized therapy in PCa is reviewed as well.

Keywords: Stat5a/b, Jak2, Stat3, survival, proliferation, prostate cancer, therapy development, surgery, radiation therapy, metastasis, caveolin, prolactin, placental lactogen, estrogen, androgen, androgen deprivation therapy.