Role of the Bone Microenvironment in the Development of Painful Complications of Skeletal Metastases

Abstract

Cancer-induced bone pain (CIBP) is the most common and painful complication in patients with bone metastases. It causes a significant reduction in patient quality of life. Available analgesic treatments for CIBP, such as opioids that target the central nervous system, come with severe side effects as well as the risk of abuse and addiction. Therefore, alternative treatments for CIBP are desperately needed. Although the exact mechanisms of CIBP have not been fully elucidated, recent studies using preclinical models have demonstrated the role of the bone marrow microenvironment (e.g., osteoclasts, osteoblasts, macrophages, mast cells, mesenchymal stem cells, and fibroblasts) in CIBP development. Several clinical trials have been performed based on these findings. CIBP is a complex and challenging condition that currently has no standard effective treatments other than opioids. Further studies are clearly warranted to better understand this painful condition and develop more effective and safer targeted therapies.

Targeting cathepsin K diminishes prostate cancer establishment and growth in murine bone

“…PCa skeletal metastases cause significant complications including severe bone pain, impaired mobility, pathological fracture, spinal cord compression and hypercalcemia (Park et al 2018). Emerging evidence shows that cysteine proteases have been implicated in the progression of tumors and in various critical tumor biological processes, including tumor cell aberrant proliferation and apoptosis, tumor cell-induced angiogenesis, as well as invasion of surrounding tissues and metastasis by malignant cells, suggesting that they are relevant to drug targets for treating cancer (Turk et al 2004).…”

Prostatic calculi cause osteoblastic immunophenotype of prostate cancer

“…These compounds have a direct effect on the osteogenesis in metastasis foci of PGC and possibly PC development in PGC tissue [8]. Similar substances, other than prostate specific antigen, also have been found in bone tissue [9,10]. Thus, the phenomenon of osteomimicry (the development of the "osteoblastic phenotype" of tumor cells as an adaptive mechanism) occurs [11].…”

Bone Metastasis Pain, from the Bench to the Bedside

“…Among these, cancer-induced bone pain (CIBP) is one of the most prevalent, presenting as movement-related, constant or most commonly, in combination [60]. Bone metastases can then induce CIBP in several ways, many of which are still under investigation [61,62]. Indeed, bone is a richly innervated tissue, and sensitive neurons can be found in both the periosteum [63,64] and the bone marrow [65,66].…”