BACKGROUND Black raspberries (BRB) inhibit a broad range of cancers in preclinical models, including in vivo models of oral, esophageal, colon, breast and skin cancer. Promising preclinical results have led to clinical evaluations in cancer patients or patients at increased risk for cancer development. OBJECTIVE To summarize clinical investigations targeting cancer or precancerous lesions with BRB and discuss future directions. METHODS A thorough literature search was conducted through December 1, 2015 to identify all published studies evaluating BRB in cancer focused clinical trials. RESULTS Research investigating BRB in clinical settings report positive effects on preneoplastic lesions or cancers of the oral cavity, esophagus and colon. BRB treatment resulted in: histologic regression of oral intraepithelial neoplasia associated with improved histologic grade and significantly reduced loss of heterozygosity at tumor suppressor gene loci, modulated genes linked to RNA processing and growth factor recycling; in the colon, BRB inhibited FAP-associated polyp progression, demethylated tumor suppressor genes and improved plasma cytokine profiles; in Barrett’s patients, BRB consumption increased tissue levels of GST-pi and decreased 8-isoprostane, a marker of lipid peroxidation/oxidative stress. CONCLUSIONS The precise dose, duration and optimum mode of BRB delivery for cancer inhibition remains to be fully elucidated. Common themes across studies support that BRB are anti-proliferative, anti- inflammatory, reduce oxidative stress and restore tumor suppressive activity. Future directions are included in the conclusions section.

中文翻译：

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癌症临床试验中的黑树莓：过去、现在和未来

背景黑树莓(BRB) 在临床前模型中抑制广泛的癌症，包括口腔癌、食道癌、结肠癌、乳腺癌和皮肤癌的体内模型。有希望的临床前结果已导致对癌症患者或癌症发展风险增加的患者进行临床评估。目的总结BRB针对癌症或癌前病变的临床研究，并讨论未来的方向。方法 进行了截至 2015 年 12 月 1 日的彻底文献检索，以找出所有已发表的在癌症重点临床试验中评估 BRB 的研究。结果 在临床环境中调查 BRB 的研究报告了对口腔癌、食道癌和结肠癌的肿瘤前病变或癌症的积极影响。BRB 处理导致：口腔上皮内瘤变的组织学消退与改善的组织学分级和显着减少肿瘤抑制基因位点的杂合性丢失、与 RNA 加工和生长因子再循环相关的调节基因有关；在结肠中，BRB 抑制 FAP 相关息肉进展、去甲基化肿瘤抑制基因和改善血浆细胞因子谱；在 Barrett 患者中，BRB 消耗增加了 GST-pi 的组织水平并降低了 8-异前列烷，这是脂质过氧化/氧化应激的标志物。结论 用于癌症抑制的 BRB 递送的精确剂量、持续时间和最佳模式仍有待充分阐明。研究中的共同主题支持 BRB 具有抗增殖、抗炎、减少氧化应激和恢复肿瘤抑制活性。