Institute of Cancer Medicine, University of Liverpool, UK.
The Countess of Chester Hospital NHS Foundation Trust, Chester, UK.
Eur J Surg Oncol. 2021 Jun;47(6):1252-1257. doi: 10.1016/j.ejso.2020.12.009. Epub 2020 Dec 18.
The treatment of pelvic malignancies has continued to improve over recent years, with neoadjuvant radiotherapy often considered the gold standard to downstage disease. Radiosensitisers are routinely employed in an attempt to improve response of cancers to radiotherapy. Previous preclinical evidence has suggested a role for metformin, a commonly used drug for type 2 diabetes.
A literature search was performed for published full text articles using the PubMed, Cochrane and Scopus databases using the search criteria string 'Metformin' AND ('Radiosensitivity' OR 'radiosensitising' OR 'radiosensitising'). Additional papers were detected by scanning the references of relevant papers. Data were extracted from each study by two authors onto a dedicated proforma. The review was registered on the PROSPERO database (ID: CRD42020199066).
A total of 242 papers were identified, 11 of which were included in this review; an additional 5 papers were obtained from reference searches. Metformin has been demonstrated to reduce cell-viability post-radiotherapy in both rectal and prostate cancer cell lines, with an enhanced effect in tumours with a p53 mutation and increased apoptosis post-radiotherapy for cervical cancer. Clinical trials demonstrate improved tumour and nodal downstaging and pCR rates for rectal cancer using metformin as a radiosensitiser.
With an increasing understanding of the underlying mechanism of the effects on metformin prospective studies are required to assess the effect of routine use on cancer related outcomes. Progressive future studies may be better served by the use of predictive biomarker guided treatment to enable identification of the appropriate cohort to target.
近年来，盆腔恶性肿瘤的治疗不断取得进展，新辅助放疗常被认为是降期疾病的金标准。增敏剂通常被用于提高癌症对放疗的反应。先前的临床前证据表明二甲双胍（一种用于 2 型糖尿病的常用药物）可能具有作用。
使用 PubMed、Cochrane 和 Scopus 数据库，使用搜索词“Metformin”和（“Radiosensitivity”或“radiosensitising”或“radiosensitising”），对已发表的全文文章进行文献检索。通过扫描相关文献的参考文献，发现了更多的文献。由两名作者将数据从每篇研究中提取到专门的表格中。该综述在 PROSPERO 数据库（ID：CRD42020199066）上进行了注册。
共确定了 242 篇论文，其中 11 篇被纳入本综述；通过参考文献检索又获得了 5 篇论文。二甲双胍已被证明可降低直肠和前列腺癌细胞系放疗后的细胞活力，在具有 p53 突变的肿瘤和放疗后细胞凋亡增加的情况下效果增强。临床试验表明，使用二甲双胍作为增敏剂可改善直肠癌的肿瘤和淋巴结降期以及 pCR 率。
随着对二甲双胍作用机制的深入了解，需要进行前瞻性研究来评估其作为常规增敏剂对癌症相关结局的影响。未来的研究可能会更好地受益于使用预测生物标志物指导治疗，以确定合适的目标人群。
