Black raspberries in cancer clinical trials: Past, present and future.

Background: Black raspberries (BRB) inhibit a broad range of cancers in preclinical models, including 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.