Human kallikrein-related peptidase-2 (hK2) and prostate cancer

Human kallikrein-related peptidase-2 (hK2)

• is abundantly expressed in malignant prostatic tissue, and its gene, KLK2, is regulated by the androgen receptor (AR)
• both PSA and hK2 are serine proteases, encoded by the human kallikrein genes KLK3 and KLK2 located on chromosome 19, respectively, and are well characterized as AR-regulated genes
• PSA and hK2 antigens are abundantly expressed in malignant prostate tissue throughout all clinical stages (1)
• the four-kallikrein (4K) panel which consists of blood measures of total, free, and intact PSA and human kallikrein-related peptidase 2 (hK2), has been demonstrated to improve detection of aggressive prostate cancer (PCa) compared to PSA among men with moderately elevated PSA levels (2)
  • has shown superior discriminative ability of the 4K panel over PSA for overall and aggressive PCa across multiethnic populations
• has been shown to reduce the number of men referred to biopsy, while retaining sensitivity for high-grade cancer (3)

Reference:

1. Timmermand, O.V., Ulmert, D., Evans-Axelsson, S. et al. Preclinical imaging of kallikrein-related peptidase 2 (hK2) in prostate cancer with a 111In-radiolabelled monoclonal antibody, 11B6. EJNMMI Res4, 51 (2014). https://doi.org/10.1186/s13550-014-0051-5
2. Darst BF, Chou A, Wan P, Pooler L, Sheng X, Vertosick EA, Conti DV, Wilkens LR, Le Marchand L, Vickers AJ, Lilja HG, Haiman CA. The Four-Kallikrein Panel Is Effective in Identifying Aggressive Prostate Cancer in a Multiethnic Population. Cancer Epidemiol Biomarkers Prev. 2020 Jul;29(7):1381-1388.
3. Auvinen A, Tammela TLJ, Mirtti T, et al. Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial. JAMA. Published online April 06, 2024. doi:10.1001/jama.2024.3841