Molecular Mechanisms of Bone Metastasis: Which Targets Came from the Bench to the Bedside?
Bone metastases ultimately result from a complex interaction between cancer cells and bone microenvironment. However, prior to the colonization of the bone, cancer cells must succeed through a series of steps that will allow them to detach from the primary tumor, enter into circulation, recognize and adhere to specific endothelium, and overcome dormancy. We now know that as important as the metastatic cascade, tumor cells prime the secondary organ microenvironment prior to their arrival, reflecting the existence of specific metastasis-initiating cells in the primary tumor and circulating osteotropic factors. The deep comprehension of the molecular mechanisms of bone metastases may allow the future development of specific anti-tumoral therapies, but so far the approved and effective therapies for bone metastatic disease are mostly based in bone-targeted agents, like bisphosphonates, denosumab and, for prostate cancer, radium-223. Bisphosphonates and denosumab have proven to be effective in blocking bone resorption and decreasing morbidity; furthermore, in the adjuvant setting, these agents can decrease bone relapse after breast cancer surgery in postmenopausal women. In this review, we will present and discuss some examples of applied knowledge from the bench to the bed side in the field of bone metastasis.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal. scasimiro@medicina.ulisboa.pt.
Sandra
S
Casimiro
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal. ajrsferreira@medicina.ulisboa.pt.|Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, 1649-028 Lisbon, Portugal. ajrsferreira@medicina.ulisboa.pt.
Arlindo R
AR
Ferreira
Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, 1649-028 Lisbon, Portugal. andre.mansinho@chln.min-saude.pt.
André
A
Mansinho
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal. ialho@medicina.ulisboa.pt.
Irina
I
Alho
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal. luiscosta.oncology@gmail.com.|Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, 1649-028 Lisbon, Portugal. luiscosta.oncology@gmail.com.
Luis
L
Costa
D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D000069448:Denosumab / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D011883:Radium / Q000627:therapeutic use
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000069448:Denosumab; D011883:Radium
bisphosphonates; bone metastases; bone-targeted agents; denosumab; osteotropic factors; pre-metastatic niche; radium-223; vicious cycle of bone metastases