Kallikrein-related peptidases (KLKs): a gene family of novel cancer biomarkers

Early diagnosis of cancer and early detection of relapse following surgery are critical for the effective treatment of the disease and for a positive clinical outcome. Identification of novel diagnostic, prognostic and predictive biomarkers will contribute utmost to clinical decision-making. The human tissue kallikrein and kallikrein-related peptidases (KLKs), encoded by the largest contiguous cluster of protease genes in the human genome, are secreted serine proteases with diverse expression patterns and physiological roles. The aberrant expression of KLKs in various malignancies as well as their involvement in many cancer-related processes, such as cell growth regulation, angiogenesis, invasion, and metastasis, has prompted scientists to investigate their potential as cancer biomarkers. Expression of distinct KLKs is associated with clinicopathological parameters of cancer patients. Moreover, several KLKs possess significant favorable or unfavorable prognostic value in various malignancies, with prostate-specific antigen (PSA) being the most widely used biomarker in clinical practice, today. KLKs are also considered as very promising biomarkers for cancer personalized medicine, especially for prediction and monitoring of patients' response to chemotherapy, therefore opening up new horizons towards effective patient monitoring post-treatment. This review describes the current status of KLKs as tumor biomarkers.