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Meldola, Italy

Santini D.,Biomedical University of Rome | Virzi V.,Biomedical University of Rome | Fratto M.E.,Biomedical University of Rome | Bertoldo F.,University of Verona | And 5 more authors.
Current Cancer Drug Targets | Year: 2010

New emerging data suggest that bisphosphonates may exert antitumor properties. Preclinical studies have demonstrated that zoledronic acid (ZA) can induce direct and indirect antitumor activities such as inhibition of angiogenesis, invasion and adhesion of tumor cells, and overall tumor progression, stimulation of adoptive and innate immunity and emerging evidence suggests that the use of these agents may prevent the development of skeletal and extra skeletal metastases. This review will critically describe the new growing evidence of antitumor activity exerted by bisphosphonates in cancer patients, both in metastatic disease and in the adjuvant setting. The effects of bisphosphonates on survival in metastatic cancer patients will be described and evidence from retrospective analyses and prospective studies will be critically reported. The early evidence from prospective analyses of survival impact by ZA in the adjuvant setting in breast cancer will be discussed together with the recently published results of the ABCSG-12 study. A new "era" for bisphosphonates in the oncological setting is opening. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of adjuvant and metastatic cancer therapies. © 2010 Bentham Science Publishers Ltd.

Santini D.,Biomedical University of Rome | Tampellini M.,University of Turin | Vincenzi B.,Biomedical University of Rome | Ibrahim T.,Osteo oncology Center | And 29 more authors.
Annals of Oncology | Year: 2012

Background: Data are limited regarding bone metastases from colorectal cancer (CRC). The objective of this study was to survey the natural history of bone metastasis in CRC. Patients and methods: This retrospective, multicenter, observational study of 264 patients with CRC involving bone examined cancer treatments, bone metastases characteristics, skeletal-related event (SRE) type and frequency, zoledronic acid therapy, and disease outcomes. Results: Most patients with bone metastases had pathologic T3/4 disease at CRC diagnosis. The spine was the most common site involved (65%), followed by hip/pelvis (34%), long bones (26%), and other sites (17%). Median time from CRC diagnosis to bone metastases was 11.00 months; median time to first SRE thereafter was 2.00 months. Radiation and pathologic fractures affected 45% and 10% of patients, respectively; 32% of patients had no reported SREs. Patients survived for a median of 7.00 months after bone metastases diagnosis; SREs did not significantly affect survival. Subgroup analyses revealed that zoledronic acid significantly prolonged median time to first SRE (2.00 months versus 1.00 month, respectively, P = 0.009) and produced a trend toward improved overall survival versus no zoledronic acid. Conclusion: This study illustrates the burden of bone metastases from CRC and supports the use of zoledronic acid in this setting. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Ibrahim T.,Osteo oncology Center | Flamini E.,Osteo oncology Center | Mercatali L.,Osteo oncology Center | Sacanna E.,Osteo oncology Center | And 2 more authors.
Cancer | Year: 2010

Prostate cancer is the second leading cause of cancer-related death in men. A typical feature of this disease is its ability to metastasize to bone. It is mainly osteosclerotic, and is caused by a relative excess of osteoblast activity, leading to an abnormal bone formation. Bone metastases are the result of a complex series of steps that are not yet fully understood and depend on dynamic crosstalk between metastatic cancer cells, cellular components of the bone marrow microenvironment, and bone matrix (osteoblasts and osteoclasts). Prostate cancer cells from primary tissue undergo an epithelial-mesenchymal transition to disseminate and acquire a bone-like phenotype to metastasize in bone tissue. This review discusses the biological processes and the molecules involved in the progression of bone metastases. Here we focus on the routes of osteoblast differentiation and activation, the crosstalk between bone cells and tumor cells, and the molecules involved in these processes that are expressed by both osteoblasts and tumor cells. Furthermore, this review deals with the recently elucidated role of osteoclasts in prostate cancer bone metastases. Certainly, to better understand the underlying mechanisms of bone metastasis and so improve targeted bone therapies, further studies are warranted to shed light on the probable role of the premetastatic niche and the involvement of cancer stem cells. © 2010 American Cancer Society.

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