Aberrant levels of
kallikrein-related
peptidases (KLK1-15) have been linked to
cancer cell proliferation, invasion and
metastasis. In
ovarian cancer, the KLK proteolytic network has a crucial role in the tissue and tumor microenvironment. Publically available
ovarian cancer genome and expression data from multiple patient cohorts show an upregulation of most KLKs. Areas covered: Here, we review the expression levels of all 15 members of this family in normal and
ovarian cancer tissues, categorizing them into highly and moderately or weakly expressed KLKs, and their association with patient prognosis and survival. We summarize their
tumor-biological functions determined in cell-based assays and xenograft models, further highlighting their suitability as
cancer biomarkers and attractive candidates for drug development. Finally, we discuss some different pharmaceutical approaches, including
peptide-based and small molecule inhibitors,
cyclic peptides,
depsipeptides, engineered natural inhibitors,
antibodies,
RNA/
DNA-based aptamers,
prodrugs,
miRNA and
siRNA. Expert opinion: In light of the results from clinical and
tumor-biological studies, together with the available pharmaceutical tools, we suggest KLK4, KLK5, KLK6 and possibly KLK7 as preferred targets for inhibition in
ovarian cancer.