Impact of STAT Proteins in Tumor Progress and Therapy Resistance in Advanced and Metastasized Prostate Cancer

SIMPLE SUMMARY: Prostate cancer (PCa) is the second most common cancer in men and one of the leading causes of death. Signal transducers and activators of transcription (STATs) are transcription factors involved in the development and progression of several cancers, including PCa. STATs play a crucial role in the therapeutic resistance of prostate cancer, including antiandrogens and chemotherapy. They are further involved in metastatic PCa and are associated with advanced and high-grade PCa. To this day, inhibitors of STATs and their signaling molecules were tested in PCa but failed to succeed in clinical trials. This review discusses different functions of STATs in PCa and the current state of STAT-inhibitors in clinical trials. ABSTRACT: Signal transducers and activators of transcription (STATs) are a family of transcription factors involved in several biological processes such as immune response, cell survival, and cell growth. However, they have also been implicated in the development and progression of several cancers, including prostate cancer (PCa). Although the members of the STAT protein family are structurally similar, they convey different functions in PCa. STAT1, STAT3, and STAT5 are associated with therapy resistance. STAT1 and STAT3 are involved in docetaxel resistance, while STAT3 and STAT5 are involved in antiandrogen resistance. Expression of STAT3 and STAT5 is increased in PCa metastases, and together with STAT6, they play a crucial role in PCa metastasis. Further, expression of STAT3, STAT5, and STAT6 was elevated in advanced and high-grade PCa. STAT2 and STAT4 are currently less researched in PCa. Since STATs are widely involved in PCa, they serve as potential therapeutic targets. Several inhibitors interfering with STATs signaling have been tested unsuccessfully in PCa clinical trials. This review focuses on the respective roles of the STAT family members in PCa, especially in metastatic disease and provides an overview of STAT-inhibitors evaluated in clinical trials.