Zoledronic acid: an unending tale for an antiresorptive agent

被引:52
作者
Caraglia, Michele [1 ]
Marra, Monica [1 ]
Naviglio, Silvio [1 ]
Botti, Gerardo [2 ]
Addeo, Raffaele [3 ]
Abbruzzese, Alberto [1 ]
机构
[1] Univ Naples 2, Dept Biochem & Biophys, I-80138 Naples, Italy
[2] Fdn G Pascale, Ist Nazl Tumori, Pathol Unit, Naples, Italy
[3] S Giovanni Dio Hosp, UOC Oncol, Naples, Italy
关键词
anticancer; breast cancer; Cyr61; cytotoxic drugs; metronomic; pharmacokinetic; prostate cancer; tipifarnib; zoledronic acid; DELTA-T-CELLS; ENDOTHELIAL GROWTH-FACTOR; ADVANCED BREAST-CANCER; LONG-TERM EFFICACY; PROSTATE-CANCER; BONE METASTASIS; SKELETAL COMPLICATIONS; MULTIPLE-MYELOMA; IN-VITRO; PREVENTIVE MEASURES;
D O I
10.1517/14656560903485664
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Importance of the field: Therapy with zoledronic acid (ZOL) is a standard for patients with malignant bone disease. However, the antitumor effects of ZOL are demonstrated only in the preclinical setting and, therefore, they require pharmacological and molecular optimization. ZOL blocks protein isoprenylation, a pleiotropic and basic biochemical process within the cells regulating the activity of several proteins involved in survival and proliferating pathways. Areas covered in this review. The present review will cover different areas of research from pharmacology to cell biology and molecular biology regarding both direct and indirect anticancer effects of ZOL in humans. The challenge in demonstrating the clinical activity of ZOL is mainly based on its pharmacokinetic properties, which are discussed in detail. What the reader will gain: New data about the modes to overcome the limitations of ZOL and the following therapeutic strategies to implement its anticancer activity are described: i) development of pharmacological combinations; ii) finding of new molecular targets of ZOL; and iii) development of new pharmacological formulations of ZOL. Take home message: In conclusion, ZOL has still underestimated anticancer properties that require further investigation in both preclinical and clinical settings.
引用
收藏
页码:141 / 154
页数:14
相关论文
共 94 条
[1]   Zoledronate inhibits αvβ3 and αvβ5 integrin cell surface expression in endothelial cells [J].
Bellahcene, A. ;
Chaplet, M. ;
Bonjean, K. ;
Castronovo, V. .
ENDOTHELIUM-JOURNAL OF ENDOTHELIAL CELL RESEARCH, 2007, 14 (02) :123-130
[2]  
Boissier S, 2000, CANCER RES, V60, P2949
[3]  
BONJEAN K, 2001, P AM ASSOC CANC RES, V42, P576
[4]  
BRUBAKER KD, 2006, BMC CANCER, V17, P6
[5]  
Caccamo N, 2008, EXPERT OPIN BIOL TH, V8, P875, DOI [10.1517/14712598.8.7.875, 10.1517/14712598.8.7.875 ]
[6]   Emerging anti-cancer molecular mechanisms of aminobisphosphonates [J].
Caraglia, M ;
Santini, D ;
Marra, M ;
Vincenzi, B ;
Tonini, G ;
Budillon, A .
ENDOCRINE-RELATED CANCER, 2006, 13 (01) :7-26
[7]   The farnesyl transferase inhibitor R115777 (Zarnestra®) synergistically enhances growth inhibition and apoptosis induced on epidermoid cancer cells by Zoledronic acid (Zometa®) and Pamidronate [J].
Caraglia, M ;
D'Alessandro, AM ;
Marra, M ;
Giuberti, G ;
Vitale, G ;
Viscomi, C ;
Colao, A ;
Del Prete, S ;
Tagliaferri, P ;
Tassone, P ;
Budillon, A ;
Venuta, S ;
Abbruzzese, A .
ONCOGENE, 2004, 23 (41) :6900-6913
[8]  
CARAGLIA M, 2005, CANCER CHEMOTH PHARM, V12, P1
[9]   R115777 (Zarnestra®)/Zoledronic acid (Zometa®) cooperation on inhibition of prostate cancer proliferation is paralleled by Erk/Akt inactivation and reduced Bcl-2 and bad phosphorylation [J].
Caraglia, Michele ;
Marra, Monica ;
Leonetti, Carlo ;
Meo, Giuseppina ;
D'Alessandro, Anna Maria ;
Baldi, Alfonso ;
Santini, Danele ;
Tonini, Giuseppe ;
Bertieri, Raffaello ;
Zupi, Gabriella ;
Budillon, Alfredo ;
Abbruzzese, Alberto .
JOURNAL OF CELLULAR PHYSIOLOGY, 2007, 211 (02) :533-543
[10]   From conventional to stealth liposomes: a new frontier in cancer chemotherapy [J].
Cattel, L ;
Ceruti, M ;
Dosio, F .
JOURNAL OF CHEMOTHERAPY, 2004, 16 :94-97