The Archives of Bone and Joint Surgery

The Archives of Bone and Joint Surgery

Newly Released Advances in the Molecular Mechanisms of Osseous Metastasis and Potential Therapeutic Strategies

Document Type : CURRENT CONCEPTS REVIEW

Authors
E. Carlos RODRIGUEZ-MERCHAN 1
Manuel Peleteiro-Pensado 2
1 Department of Orthopaedic Surgery, La Paz University Hospital, Madrid, Spain
2 Department of Orthopedic Surgery, La Paz University Hospital, Madrid, Spain
10.22038/abjs.2022.57856.2865
Abstract
The appearance of bone metastases (BM) in individuals with advanced solid cancers (breast, prostate, lung) often 
worsens their quality of life and prognosis. Although none have been fully effective, several strategies have been used 
to combat BM. Hence, the need for new data that could be useful for treating bone metastasis. To this end, we reviewed 
the recent literature on the subject. About patients with prostate cancer, treatments with PIP5K1α inhibitors have been 
found to inhibit tumor invasion and metastasis, and G protein-coupled receptor class C group 5 member A (GPRC5A) 
could be a future therapeutic target. Regarding patients with breast cancer, we found the following: Asperolide A could 
be another curative drug; targeting transforming growth factor-beta (TGFβ) and bone morphogenetic protein (BMP) 
signaling pathways, along with osteoclast activity, could be a favorable therapeutic approach in the preclusion of osteolytic bone destruction; TRAF6 inhibitors such as 6877002 appear promising; aiming the BMP4-SMAD7 signaling axis 
is an innovative therapeutic approach; there is favorable proof for the plausible therapeutic utilization of bone aiming 
immunostimulatory MOF (BT-isMOF) nanoparticles, and inhibition of IL4R and macrophages could have therapeutic 
benefits. For lung cancer, the function of LIGHT in osteolytic osseous illness instigated by metastatic non-small cell lung 
cancer should be highlighted. 
Level of evidence: III
Keywords
Breast cancer
Bone
Lung cancer
Metastasis
Prostate cancer
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The Archives of Bone and Joint Surgery
Volume 10, Issue 9
September 2022
Pages 741-755

  • Receive Date 19 May 2021
  • Revise Date 12 February 2022
  • Accept Date 15 February 2022