Protease Inhibitor Kazal Type 1 as a Driver of Ovarian Cancer Progression
Ovarian tumor specimens showing SPINK1 staining. Development of SPINK1 as a tissue biomarker may enable identification of patients able to benefit from molecularly targeted therapies.
Serine protease inhibitor Kazal type 1 (SPINK1) is a trypsin inhibitor whose biological role is to protect the pancreas, where trypsin and other digestive enzymes are produced. However, SPINK1 is also produced by certain tumor types, where it is correlated with aggressive tumor behavior.
Dr. Radisky's Proteases in Cancer Laboratory has discovered that SPINK1 produced by ovarian tumors is a marker for poor patient prognosis. SPINK1 promotes survival of detached tumor cells by inhibiting proteases. This mechanism can facilitate tumor metastasis. SPINK1 also promotes the proliferation of ovarian cancer cells through activation of epidermal growth factor receptor (EGFR) signaling.
Dr. Radisky's team is working to unravel the pathways by which SPINK1 promotes ovarian cancer growth and progression in order to help identify new avenues for therapy. Efforts are also underway to define the subset of ovarian cancers in which these pathways are most important, which could help identify which patients are most able to benefit from therapies that target SPINK1 pathways.