Background: Recent reports indicate that the tumor microenvironment plays a pivotal role
in cancer development and progression, leading to a paradigm shift in the way cancer is studied and
targeted. In contrast to traditional approaches, where only tumor cells are targeted for the treatment, an
emerging approach is to develop therapeutics which target the tumor microenvironment while complementing
or enhancing current treatments. Legumain (LGMN) is a newly identified target which is
highly expressed in the tumor microenvironment and in tumor cells, and holds potential both as a
biomarker and as a therapeutic target.
Conclusion: This review will be the first to summarize the expression of LGMN in common cancers,
as well as its roles in tumorigenesis and metastasis. This review also discusses the current developments
and future prospects of targeting LGMN through the development of DNA vaccines, azopeptides,
small molecule inhibitors and LGMN activated prodrugs, highlighting the potential of LGMN as
a target for cancer therapeutics.