Santini D, Vespasiani Gentilucci U, Vincenzi B, Picardi A, Vasaturo F, La Cesa A, Onori N, Scarpa S, Tonini G
Interdisciplinary Center for Biomedical Research (CIR), Oncology, University Campus Bio-Medico, Rome, Italy.
Ann Oncol. 2003 Oct;14(10):1468-76. doi: 10.1093/annonc/mdg401.
Bisphosphonates are now well established as successful agents for the prevention and treatment of postmenopausal osteoporosis, corticosteroid-induced bone loss and Paget's disease. Bisphosphonates have also recently become important in the management of cancer-induced bone disease, and they now have a widely recognized role for patients with multiple myeloma and bone metastases secondary to breast cancer and prostate cancer. Recent studies suggest that, besides the strong antiosteoclastic activity, the efficacy of such compounds in the oncological setting could also be due also to direct antitumor effect, exerted at different levels. Here, after a brief analysis of the chemical structure, we will review the antineoplastic and biological properties of bisphosphonates. We will start from well estabilished mechanisms of action and go on to discuss the latest evidence and hypotheses. In particular, we will review the antiresorptive properties in malignant osteolysis and the recent evidence of a direct antitumor effect. Furthermore, this review will analyze the influence of bisphosphonates on cancer growth factor release, their effect on cancer cell adhesion, invasion and viability, the proapoptotic potential on cancer cells, the antiangiogenic effect, and, finally, the immunomodulating properties of bisphosphonates on the gammadelta T cell population.
双膦酸盐现已成为预防和治疗绝经后骨质疏松症、糖皮质激素诱导的骨质流失和佩吉特病的成功药物。双膦酸盐最近在癌症诱导的骨病管理中也变得很重要，并且它们现在对于患有多发性骨髓瘤以及继发于乳腺癌和前列腺癌的骨转移患者具有广泛认可的作用。最近的研究表明，除了强大的抗破骨细胞活性外，此类化合物在肿瘤学环境中的疗效也可能归因于在不同水平发挥作用的直接抗肿瘤作用。在此，在简要分析化学结构之后，我们将综述双膦酸盐的抗肿瘤和生物学特性。我们将从已确立的作用机制开始，进而讨论最新的证据和假说。特别是，我们将综述在恶性骨溶解中的抗吸收特性以及直接抗肿瘤作用的最新证据。此外，本综述将分析双膦酸盐对癌症生长因子释放的影响、它们对癌细胞黏附、侵袭和活力的影响、对癌细胞的促凋亡潜力、抗血管生成作用，以及最后双膦酸盐对γδ T细胞群体的免疫调节特性。
