Christodoulou Maria-Ioanna, Scorilas Andreas
Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
Curr Med Chem. 2017;24(1):14-56. doi: 10.2174/0929867323666160907161459.
Metformin, a natural product from Galega officinalis, is an oral drug, now in the forefront of the therapeutic management of type-2 diabetes mellitus. A series of clinical observations of the last decades, support that metformin may contribute to lowering the risk of cancer development in diabetic patients, and also to improvement of response-to-therapy and survival in individuals with certain types of malignancies. Moreover, several preclinical in vitro and in vivo data indicate that metformin indeed exerts anti-proliferative capacities upon tumor cells mediated through a variety of mechanisms. Interestingly, metformin has been shown to act in synergy with certain anti-cancer agents and also to overcome chemo- and/or radio-resistance of various types of tumors, providing a hopeful rationale for novel therapeutic strategies against cancer development and progression. However, this remains an issue of controversy, since significant contradictions exist among the available data. Limitations of preclinical studies and caveats of epidemiological works, together with significant variances among the several types of cancer and the fact that the mode of metformin's action is largely unknown, make longitudinal surveys urgently needed. Now, a plethora of large clinical trials are active worldwide, aiming at determining the effect of metformin in the prevention or prognosis of a variety of human cancers. If encouraging results arise, metformin will be an attractive candidate adjuvant in the management of human neoplasias, due to its safety, tolerability and low-cost, expected to mitigate adverse effects and no-response parameters of current anti-cancer therapeutics, thus improving the quality of life and survival of cancer patients.
二甲双胍是一种从山羊豆中提取的天然产物，是一种口服药物，目前处于2型糖尿病治疗管理的前沿。过去几十年的一系列临床观察表明，二甲双胍可能有助于降低糖尿病患者患癌风险，还能改善某些类型恶性肿瘤患者的治疗反应和生存率。此外，一些临床前的体外和体内数据表明，二甲双胍确实通过多种机制对肿瘤细胞发挥抗增殖作用。有趣的是，二甲双胍已被证明能与某些抗癌药物协同作用，还能克服各种类型肿瘤的化疗和/或放疗耐药性，为对抗癌症发生和进展的新治疗策略提供了有希望的理论依据。然而，这仍然是一个有争议的问题，因为现有数据存在重大矛盾。临床前研究的局限性和流行病学研究的注意事项，加上几种癌症之间的显著差异以及二甲双胍的作用模式很大程度上未知，使得迫切需要进行纵向调查。现在，全球范围内有大量大型临床试验正在进行，旨在确定二甲双胍对各种人类癌症预防或预后的影响。如果出现令人鼓舞的结果，由于其安全性、耐受性和低成本，二甲双胍将成为人类肿瘤管理中一个有吸引力的候选辅助药物，有望减轻当前抗癌治疗的不良反应和无反应参数，从而提高癌症患者的生活质量和生存率。
