Last generation of amino-bisphosphonates (N-BPs) and cancer angio-genesis: a new role for these drugs?
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 anti-angiogenic 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.
Santini
Daniele
D
Medical Oncology, University Campus Bio-Medico, Rome. d.santini@unicampus.it
Schiavon
Gaia
G
Angeletti
Silvia
S
Vincenzi
Bruno
B
Gasparro
Simona
S
Grilli
Claudia
C
La Cesa
Annalisa
A
Virzí
Vladimir
V
Leoni
Valentina
V
Budillon
Alfredo
A
Addeo
Santolo R
SR
Caraglia
Michele
M
Dicuonzo
Giordano
G
Tonini
Giuseppe
G
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D004164:Diphosphonates / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D008798:Mevalonic Acid / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010330:Patents as Topic; D012039:Regional Blood Flow / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
D020533:Angiogenesis Inhibitors; D004164:Diphosphonates; D008798:Mevalonic Acid