TY - JOUR
T1 - Last generation of amino-bisphosphonates (N-BPs) and cancer angiogenesis
T2 - A new role for these drugs?
AU - Santini, Daniele
AU - Schiavon, Gaia
AU - Angeletti, Silvia
AU - Vincenzi, Bruno
AU - Gasparro, Simona
AU - Grilli, Claudia
AU - La Cesa, Annalisa
AU - Virzí, Vladimir
AU - Leoni, Valentina
AU - Budillon, Alfredo
AU - Addeo, Santolo R.
AU - Caraglia, Michele
AU - Dicuonzo, Giordano
AU - Tonini, Giuseppe
PY - 2006
Y1 - 2006
N2 - Bisphosphonate (BPs) therapy has become a standard of care for patients with malignant bone disease. In addition, preclinical and preliminary clinical data suggest that BPs exert their direct or indirect antitumoral effects on cancer growth factor release, on cancer cell adhesion, invasion and viability, on cancer angiogenesis and on cancer cell apoptosis. Here, after a brief analysis on clinical indications, on the last generation amino-bisphosphonates (N-BP) and on biochemical pathways as molecular targets of BPs, we will discuss the molecular mechanisms of these antitumor effects. Recent evidence suggests that part of the antitumor activity of bisphosphonates may be attributed to an antiangiogenic effect. For this reason, we will analyse all the in vitro and in vivo preclinical reports and the first clinical evidence of antiangiogenic activity exerted by this class of drugs. Several patents have been reported in the review, considering the recents activities observed for these drugs. Taking together all the major results obtained in the described studies, it is possible to affirm that BPs, particularly zoledronic acid and pamidronate, could potentially represent a very powerful tool for angiogenesis inhibition leading to a better control of cancer growth and progression. The translation into the clinical setting of the preclinical evidence of an antiangiogenic power of these drugs is becoming an imperative need and should represent the objective of future clinical trials.
AB - Bisphosphonate (BPs) therapy has become a standard of care for patients with malignant bone disease. In addition, preclinical and preliminary clinical data suggest that BPs exert their direct or indirect antitumoral effects on cancer growth factor release, on cancer cell adhesion, invasion and viability, on cancer angiogenesis and on cancer cell apoptosis. Here, after a brief analysis on clinical indications, on the last generation amino-bisphosphonates (N-BP) and on biochemical pathways as molecular targets of BPs, we will discuss the molecular mechanisms of these antitumor effects. Recent evidence suggests that part of the antitumor activity of bisphosphonates may be attributed to an antiangiogenic effect. For this reason, we will analyse all the in vitro and in vivo preclinical reports and the first clinical evidence of antiangiogenic activity exerted by this class of drugs. Several patents have been reported in the review, considering the recents activities observed for these drugs. Taking together all the major results obtained in the described studies, it is possible to affirm that BPs, particularly zoledronic acid and pamidronate, could potentially represent a very powerful tool for angiogenesis inhibition leading to a better control of cancer growth and progression. The translation into the clinical setting of the preclinical evidence of an antiangiogenic power of these drugs is becoming an imperative need and should represent the objective of future clinical trials.
KW - Amino-bisphosphonates
KW - Angiogenesis
KW - Anti-cancer effects
UR - http://www.scopus.com/inward/record.url?scp=39049153469&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39049153469&partnerID=8YFLogxK
U2 - 10.2174/157489206778776989
DO - 10.2174/157489206778776989
M3 - Article
C2 - 18221048
AN - SCOPUS:39049153469
VL - 1
SP - 383
EP - 396
JO - Recent Patents on Anti-Cancer Drug Discovery
JF - Recent Patents on Anti-Cancer Drug Discovery
SN - 1574-8928
IS - 3
ER -