Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Cancer Treat Rev. 2012 Aug;38(5):407-15. doi: 10.1016/j.ctrv.2011.09.003. Epub 2011 Oct 7.
The bone marrow microenvironment provides a site for cancer cells to evade systemic anticancer therapy. Dormant tumor micrometastases are believed to be the source of disease persistence and relapse; however, the exact characteristics of cancer stem cells vs. cancer cells with limited metastatic potential have yet to be elucidated. Bisphosphonates inhibit osteoclast-mediated bone resorption, are approved for treating malignant bone disease from advanced cancers, and have shown efficacy for preventing cancer treatment-induced bone loss. Altering the bone marrow microenvironment to make it less conducive to cancer cell survival is now emerging as an important means to prevent cancer recurrence. This review aims to distill the diverse literature and provide a brief overview of the numerous preclinical and early clinical studies of bisphosphonates demonstrating a variety of direct and indirect anticancer activities that affect both the tumor cell (the "seed") and surrounding microenvironment (the "soil"). Recently, zoledronic acid was found to improve disease-free survival and overall survival in some adjuvant breast cancer settings and prolonged survival in patients with multiple myeloma and other advanced cancers. In the prostate cancer setting, antiresorptive therapy was reported to delay the development of overt bone metastases. Ongoing studies will provide further insight regarding the anticancer potential of bisphosphonates and other antiresorptive agents.
骨髓微环境为癌细胞逃避全身抗癌治疗提供了场所。休眠的肿瘤微转移被认为是疾病持续存在和复发的根源；然而，癌症干细胞与转移潜力有限的癌细胞的确切特征尚未阐明。双膦酸盐抑制破骨细胞介导的骨质吸收，已被批准用于治疗晚期癌症的恶性骨病，并已显示出预防癌症治疗引起的骨质流失的疗效。改变骨髓微环境使其不利于癌细胞存活，现已成为预防癌症复发的重要手段。这篇综述旨在梳理大量文献，并简要概述双膦酸盐的众多临床前和早期临床研究，这些研究展示了各种直接和间接的抗癌活性，这些活性既影响肿瘤细胞（“种子”），也影响周围的微环境（“土壤”）。最近，唑来膦酸被发现可改善某些辅助乳腺癌治疗中的无病生存期和总生存期，并延长多发性骨髓瘤和其他晚期癌症患者的生存期。在前列腺癌治疗中，抗吸收治疗被报道可延迟明显骨转移的发生。正在进行的研究将进一步深入了解双膦酸盐和其他抗吸收剂的抗癌潜力。
