Emerging Role of IGF-1 in Prostate Cancer: A Promising Biomarker and Therapeutic Target

SIMPLE SUMMARY: Prostate cancer (PCa) affects millions of men globally, and approximately 20% of PCa patients are found after they develop into a lethal metastatic or castration-resistant state. High levels of serum insulin-like growth factor-1 (IGF-1) and activated insulin-like growth factor-1 receptor (IGF-1R) in the prostate are found in PCa. A systematical understanding of the mechanisms of IGF-1 involved in PCa progression will expedite the development of new treatment approaches. The goal of this review is to summarize the literature on the role of IGF-1 in PCa to obtain a perspective regarding future scientific endeavors on PCa diagnosis and treatment. ABSTRACT: Prostate cancer (PCa) is a highly heterogeneous disease driven by gene alterations and microenvironmental influences. Not only enhanced serum IGF-1 but also the activation of IGF-1R and its downstream signaling components has been increasingly recognized to have a vital driving role in the development of PCa. A better understanding of IGF-1/IGF-1R activity and regulation has therefore emerged as an important subject of PCa research. IGF-1/IGF-1R signaling affects diverse biological processes in cancer cells, including promoting survival and renewal, inducing migration and spread, and promoting resistance to radiation and castration. Consequently, inhibitory reagents targeting IGF-1/IGF-1R have been developed to limit cancer development. Multiple agents targeting IGF-1/IGF-1R signaling have shown effects against tumor growth in tumor xenograft models, but further verification of their effectiveness in PCa patients in clinical trials is still needed. Combining androgen deprivation therapy or cytotoxic chemotherapeutics with IGF-1R antagonists based on reliable predictive biomarkers and developing and applying novel agents may provide more desirable outcomes. This review will summarize the contribution of IGF-1 signaling to the development of PCa and highlight the relevance of this signaling axis in potential strategies for cancer therapy.