In spite of decades of research, cancer is still the second leading cause of death worldwide. Cancers are complex diseases that occur due to genetic and epigenetic changes. While current therapies have contributed to increased overall survival in cancer patients, especially with localized disease, therapies to treat the metastatic disease have been less successful. Malignant tumor cells metastasize to different distant organs, with many of the most common tumors (breast, lung, prostate) metastasizing frequently to the bone. Once tumor cells have established in the bone microenvironment through a variety of mechanisms, they alter the bone microenvironment to change the balance of bone turnover leading to an increase in bone destruction (osteolytic) and/or bone formation (osteoblastic). These changes in bone remodeling result in increased fracture risk and severe bone pain.
Bone is an active dynamic tissue that is being continuously remodeled by the concerted action of bone residential osteoblast (forms bone) and osteoclast (resorbs bone) cells where osteocyte cells embedded in the bone matrix regulate the balance between bone formation and bone resorption. In healthy bone, osteoclast-mediated bone resorption is tightly coupled to the osteoblast-mediated bone formation to maintain an appropriate bone volume. However, in diseases including osteoporosis, tumor, diabetes, and other metabolic disorder, this balance is disrupted leading to shifts in the bone volume that can result in an increased fracture.
Tumors that metastasize to bone, must have the correct mutations to allow them to invade, circulate through the bloodstream, and exit into the bone microenvironment, similar to the process that tumor cells use to metastasize to any secondary site. However, in the bone tumor cells must be able to secrete factors (such as parathyroid hormone-related protein and the interleukins) to stimulate the osteoblast to make receptor activator of NF?B Ligand (RANKL) to activate the osteoclast to resorb the bone, since tumors cannot directly resorb the bone mineral matrix. This enhanced osteoclast activity not only resorbs bone, but also releases many factors present in the embedded bone matrix (such as Transforming growth factor ß (TGF-ß), Bone morphogenetic proteins (BMPs), Wnts, and others), which further stimulate tumor cell growth and proliferation, and drive cancer cells to release more factors that further enhance osteoclast activity. Additionally, other tumors that start in the bone (osteosarcomas), invade the bone (melanoma and head and neck tumors), or reside in the marrow (myeloma and other hematological tumors) can similarly stimulate bone resorption.
In addition, tumors residing in the bone interact with many other cell types and unique structural properties of the bone microenvironment that also contribute to tumor-induced bone disease. For example, it is well-established that tumors interact with the immune compartment (myeloid cells, macrophages, and others), fibroblasts, and endothelial cells to increase tumor growth and evade immune surveillance. Additionally, tumor cells interact with the mineral components of bone to activate mechanical signaling leading to a further increase in factors that induce osteoclast differentiation. Interactions with muscles and nerve cells have also been shown to contribute to tumor-induced bone disease. Together, there is clearly a dynamic and complex series of interactions between tumors and the bone microenvironment.
A better understanding of these interactions may lead to therapeutic strategies for inhibiting tumor metastasis to bone, tumor growth, and bone destruction. Thus, an in-depth understanding of the molecular mechanism and finding a strategy for the treatment of bone metastasis are urgently required. Within this research frame, submissions are encouraged on focusing below but not limited to:
1. Studies involved in bone and cancer (both metastatic and other tumors in bone)
2. Prevention strategy for cancer-associated bone metastasis
3. Testing drugs for prevention in bone metastasis
4. Molecular mechanism involved in cancer-induced bone metastasis
5. The cross-talk between cancer cells and other cells present in bone microenvironments
6. Clinical study for cancer and bone health
