Liver Microenvironment Response to Prostate Cancer Metastasis and Hormonal Therapy

SIMPLE SUMMARY: Prostate cancer patients with disease that has invaded the liver have the worst outcomes. Within the liver, cancer cells are exposed to a unique microenvironment of liver specific cells and proteins. In general, interaction between the microenvironment and cancer is known to provide cues which alter cancer cell biology and behavior. This review aims to summarize current knowledge about the microenvironment of the liver, what predisposes prostate cancer to move to the liver, how the liver responds to prostate cancer being there, and how the liver responds to current treatment strategies. We aim to provide insight into this under-investigated area of prostate cancer research as if we can understand why liver metastasis is associated with such poor patient outcomes, we will be better placed to address this. ABSTRACT: Prostate cancer-associated deaths arise from disease progression and metastasis. Metastasis to the liver is associated with the worst clinical outcomes for prostate cancer patients, and these metastatic tumors can be particularly resistant to the currently widely used chemotherapy and hormonal therapies, such as anti-androgens which block androgen synthesis or directly target the androgen receptor. The incidence of liver metastases is reportedly increasing, with a potential correlation with use of anti-androgen therapies. A key player in prostate cancer progression and therapeutic response is the microenvironment of the tumor(s). This is a dynamic and adaptive collection of cells and proteins, which impart signals and stimuli that can alter biological processes within prostate cancer cells. Investigation in the prostate primary site has demonstrated that cells of the microenvironment are also responsive to hormones and hormonal therapies. In this review, we collate information about what happens when cancer moves to the liver: the types of prostate cancer cells that metastasize there, the response of resident mesenchymal cells of the liver, and how the interactions between the cancer cells and the microenvironment may be altered by hormonal therapy.