Bone Metastasis: Current State of Play

Abstract

Bone metastasis (BM) in cancer remains a critical issue because of its associated clinical and biological complications. Moreover, BM can alter the quality of life and survival rate of cancer patients. Growing evidence suggests that bones are a fertile ground for the development of metastasis through a “vicious circle” of bone resorption/formation and tumor growth. This review aims to outline the current major issues in the diagnosis and management of BM in the most common types of osteotropic cancers and describe the mechanisms and effects of BM. First, we discuss the incidence of BM through the following questions: Are we witnessing an increase in incidence, and are we now better equipped with modern imaging techniques? Is the advent of efficient bone resorption inhibitors affecting the bigger picture of BM management? Second, we discuss the potential effects of cancer progression and well-prescribed drugs, such as multitarget tyrosine kinase inhibitors, inhibitors of the mammalian target of rapamycin, and immune checkpoint inhibitors, on BM. Finally, we examine the duality of the effects of some therapies that may help in cancer treatment but may also contribute to further BM.

The Role of Cancer-Associated Fibroblasts in Prostate Cancer Tumorigenesis

“…Prostate adenocarcinoma predominantly forms bone metastases [20]. A possible determinant of PCa bone tropism is chemokine (C-X-C motif) receptor type-4 (CXCR4)/chemokine (C-X-C motif) ligand 12 (CXCL12) signaling [149].…”

Peptide targeting of the lysolipid-sensing GPR55 for osteoclastogenesis tuning

“…Peptide-P1 was also shown to inhibit GPR55-dependent proliferation of EHEB and DeFew cells, which are two human B-lymphoblastoid cell lines [38], and among other tumour cells, leukemic cells can metastasise at the bone level [63]. Bone metastasisation is a complex process that involves cross-talk between tumour cells and bone resident cells [64,65]. Osteoclast bone resorption is essential for metastasis establishment, as upon bone degradation, growth factors are released from the bone matrix that can stimulate metastatic cell growth and survival [66].…”

Emergence of Cancer-Associated Fibroblasts as an Indispensable Cellular Player in Bone Metastasis Process

“…Once a dormant state is disturbed, osteomimicry ensues, where cancer cells stimulate both osteoclasts and osteoblasts, thereby inducing aberrant bone remodeling [ 39 ] ( Figure 2 ). Bone metastasis lesions can be osteolytic or osteoblastic, depending on whether osteoclasts or osteoblasts are predominantly activated [ 1 ]. Moreover, osteomimicry is accompanied by a so-called vicious cycle, which consists of a positive feedback loop between aberrant bone remodeling and cancer cell proliferation [ 48 ].…”

“…Bone pain is common in patients with bone metastasis and impairs markedly their quality of life [ 1 ]. Bone-tropic breast cancer cells expressed abundantly V-ATPase and MCT4, leading to intratumoral acidosis, which induced α-SMA + FAP + CAFs, osteoblasts and MSCs to express inflammatory and nociceptive mediators including nerve growth factor, brain-derived neurotropic factor, IL-1β, IL-6, CXCL8, and CCL5 [ 114 ], which may be responsible for bone pain.…”

“…Various types of solid tumors, particularly breast, prostate and lung cancer, frequently metastasize to bone during their course and the bone is the third commonest site of metastasis after the liver and lung [ 1 ]. Metastasis proceeds through multiple steps, which consist of growth at the primary site, intravasation into the systemic circulation, dissemination via circulation, extravasation into the metastatic organ, and growth at the metastatic organ [ 2 ].…”