Page 76 - Read Online

Page 14 of 19 Maurizi et al. J Cancer Metastasis Treat 2021;7:35 https://dx.doi.org/10.20517/2394-4722.2021.74

secreted by cancer cells are potentially able to reprogram the entire bone microenvironment, including at
least osteoblasts, osteoclasts, and endothelial cells. However, what is of the utmost importance is translating
these important basic science concepts to the clinic. There has been significant attention given to how the
bone microenvironment can be targeted to reduce PMN formation, and many clinical trials have explored
the use of bone-targeting agents to prevent metastasis, with promising results. In addition, EVs hold great
promise for therapy, with many potential candidates in preclinical phase. However, since the field is very
young, there is still a long way to go to get to an EV-targeting anti-PMN therapy. Nonetheless, EVs are
incredibly powerful diagnostic and therapy-monitoring tools, as well as potential drug delivery systems,
which hold much potential for the future.

DECLARATIONS
Authors’ contributions
Collected the data, wrote the manuscript and prepared figures and tables: Maurizi A, Ponzetti M
Coordinated the work, wrote and reviewed the manuscript: Rucci N
Revised and approved the final version of the manuscript: Maurizi A, Ponzetti M, Rucci N

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by “Associazione Italiana per la Ricerca sul Cancro” (AIRC, #IG2015Id.16826) to
Rucci N and by the AIRC-FIRC fellowships to Maurizi A and Ponzetti M (# 22356 and #24019),
respectively.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2021.

REFERENCES
1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36
cancers in 185 countries. CA Cancer J Clin 2021;71:209-49. DOI PubMed
2. Güth U, Huang DJ, Dirnhofer S, Rochlitz C, Wight E. Distant metastatic breast cancer as an incurable disease: a tenet with a need for
revision. Cancer J 2009;15:81-6. DOI PubMed
3. Zijl F, Krupitza G, Mikulits W. Initial steps of metastasis: cell invasion and endothelial transmigration. Mutat Res 2011;728:23-34.
DOI PubMed PMC
4. Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889;133:571-3. PubMed
5. Gattazzo F, Urciuolo A, Bonaldo P. Extracellular matrix: a dynamic microenvironment for stem cell niche. Biochim Biophys Acta
2014;1840:2506-19. DOI PubMed PMC
6. Raaijmakers MH, Mukherjee S, Guo S, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature
2010;464:852-7. DOI PubMed PMC
7. Coleman RE. Skeletal complications of malignancy. Cancer 1997;80:1588-94. DOI PubMed
8. Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655-64. DOI PubMed
9. Wang H, Pan J, Barsky L, et al. Characteristics of pre-metastatic niche: the landscape of molecular and cellular pathways. Mol
Biomed 2021:2.