Published online Jan 21, 2016. doi: 10.3748/wjg.v22.i3.906
Peer-review started: June 12, 2015
First decision: October 14, 2015
Revised: November 5, 2015
Accepted: December 8, 2015
Article in press: December 8, 2015
Published online: January 21, 2016
Processing time: 219 Days and 12.6 Hours
Best known for their anti-resorptive activity in bone, bisphosphonates (BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor (HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups.
Core tip: Bisphosphonates demonstrate antineoplastic activity in various malignancies but have received little attention in cancers of the digestive tract. We review the preclinical and clinical experience with bisphosphonates in digestive cancers and discuss their potential therapeutic application in this disease group, particularly in the context of recent data on bisphosphonate-induced inhibition of human epidermal growth factor receptor signaling.