AKT in Bone Metastasis of Solid Tumors: A Comprehensive Review

SIMPLE SUMMARY: Bone metastasis is a frequent complication of solid tumors and leads to a reduced overall survival. Although much progress has been made in the field of tumor therapy in the last years, bone metastasis depicts a stage of the disease with a lack of appropriate therapeutical options. Hence, this review aims to present the role of AKT in bone metastasis of solid tumors to place the spotlight on AKT as a possible therapeutical approach for patients with bone metastases. Furthermore, we intended to discuss postulated underlying molecular mechanisms of the bone metastasis-promoting effect of AKT, especially in highly bone-metastatic breast, prostate, and lung cancer. To conclude, this review identified the AKT kinase as a potential therapeutical target in bone metastasis and revealed remaining questions, which need to be addressed in further research projects. ABSTRACT: Solid tumors, such as breast cancer and prostate cancer, often form bone metastases in the course of the disease. Patients with bone metastases frequently develop complications, such as pathological fractures or hypercalcemia and exhibit a reduced life expectancy. Thus, it is of vital importance to improve the treatment of bone metastases. A possible approach is to target signaling pathways, such as the PI3K/AKT pathway, which is frequently dysregulated in solid tumors. Therefore, we sought to review the role of the serine/threonine kinase AKT in bone metastasis. In general, activation of AKT signaling was shown to be associated with the formation of bone metastases from solid tumors. More precisely, AKT gets activated in tumor cells by a plethora of bone-derived growth factors and cytokines. Subsequently, AKT promotes the bone-metastatic capacities of tumor cells through distinct signaling pathways and secretion of bone cell-stimulating factors. Within the crosstalk between tumor and bone cells, also known as the vicious cycle, the stimulation of osteoblasts and osteoclasts also causes activation of AKT in these cells. As a consequence, bone metastasis is reduced after experimental inhibition of AKT. In summary, AKT signaling could be a promising therapeutical approach for patients with bone metastases of solid tumors.