1. Metastatic bone disease: Pathogenesis and therapeutic options
- Author
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Janet E. Brown, Stella D'Oronzo, Francesco Silvestris, and Robert E. Coleman
- Subjects
TKIs, TK inhibitors ,0301 basic medicine ,Oncology ,lcsh:Diseases of the musculoskeletal system ,DFS, disease-free survival ,Bone disease ,medicine.medical_treatment ,Bone targeting agents ,BTA, bone targeting agents ,GFs, growth factors ,Review Article ,Skeletal related events ,CRPC, castration-resistant PC ,PDGF, platelet-derived growth factor ,Prostate cancer ,PIs, proteasome inhibitors ,SREs, skeletal-related events ,0302 clinical medicine ,BTM, bone turnover markers ,HER-2, human epidermal growth factor receptor 2 ,PTH, parathyroid hormone ,CXCL-12, C–X–C motif chemokine-ligand-12 ,MPC, malignant plasma cells ,SSEs, symptomatic skeletal events ,TGF-β, transforming growth factor β ,DKK1, dickkopf1 ,RANK-L, receptor activator of NF-κB ligand ,MM, multiple myeloma ,N-BPs, nitrogen-containing BPs ,Bone metastasis ,RT, radiation therapy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,VEGF, vascular endothelial growth factor ,humanities ,CCR, chemokine-receptor ,PFS, progression-free survival ,ECM, extracellular matrix ,PTH-rP, PTH related protein ,Osteotropic tumors ,Denosumab ,BPs, bisphosphonates ,030220 oncology & carcinogenesis ,GAS6, growth-arrest specific-6 ,MIP-1α, macrophage inflammatory protein-1 alpha ,Adjuvant ,medicine.drug ,medicine.medical_specialty ,BC, breast cancer ,PC, prostate cancer ,BMD, bone mineral density ,EBC, early BC ,NF-κB, nuclear factor-κB ,mTOR, mammalian target of rapamycin ,LC, lung cancer ,lcsh:RC254-282 ,BM, bone metastases ,OS, overall survival ,03 medical and health sciences ,Breast cancer ,MCSF, macrophage colony-stimulating factor ,Internal medicine ,BMSC, bone marrow stromal cells ,medicine ,ET-1, endothelin-1 ,GnRH, gonadotropin-releasing hormone ,v-ATPase, vacuolar-type H+ ATPase ,VEGFR, VEGF receptor ,business.industry ,Bone metastases ,TK, tyrosine kinase ,HR, hormone receptor ,Cancer ,ONJ, osteonecrosis of the jaw ,medicine.disease ,QoL, quality of life ,FGF, fibroblast growth factor ,IL, interleukin ,BMPs, bone morphogenetic proteins ,Clinical trial ,non-N-BPs, non-nitrogen containing BPs ,PSA, prostate specific antigen ,030104 developmental biology ,FDA, food and drug administration ,TNF, tumornecrosis factor ,CXCR-4, chemokine-receptor-4 ,MCSFR, MCSF receptor ,ActRIIA, activin-A type IIA receptor ,lcsh:RC925-935 ,business ,MAPK, mitogen-activated protein kinase - Abstract
Highlights • Bone metastases negatively impact on patients’ quality of life (QoL). • Skeletal related events have a detrimental effect on both QoL and survival. • Both local and systemic treatments are often required to manage bone metastases. • Bone turnover modulators reduce the risk of skeletal complications and improve pain. • Novel agents may deserve further investigation for the management of bone metastases., Bone metastases (BM) are a common complication of cancer, whose management often requires a multidisciplinary approach. Despite the recent therapeutic advances, patients with BM may still experience skeletal-related events and symptomatic skeletal events, with detrimental impact on quality of life and survival. A deeper knowledge of the mechanisms underlying the onset of lytic and sclerotic BM has been acquired in the last decades, leading to the development of bone-targeting agents (BTA), mainly represented by anti-resorptive drugs and bone-seeking radiopharmaceuticals. Recent pre-clinical and clinical studies have showed promising effects of novel agents, whose safety and efficacy need to be confirmed by prospective clinical trials. Among BTA, adjuvant bisphosphonates have also been shown to reduce the risk of BM in selected breast cancer patients, but failed to reduce the incidence of BM from lung and prostate cancer. Moreover, adjuvant denosumab did not improve BM free survival in patients with breast cancer, suggesting the need for further investigation to clarify BTA role in early-stage malignancies. The aim of this review is to describe BM pathogenesis and current treatment options in different clinical settings, as well as to explore the mechanism of action of novel potential therapeutic agents for which further investigation is needed.
- Published
- 2019