Prostate-specific antigen (PSA) is a single-chain glycoprotein also known as γ-semioplasmin or kallikrein-3 (KLK3). PSA in blood exists in both free (f) and complexed (c) forms and is involved in semen liquefaction and sperm motility activation. PSA is a serine protease secreted by prostate epithelial cells. PSA is not only active in prostate tissue but also plays a crucial role in signaling pathways such as prostate cancer proliferation, invasion, metastasis, angiogenesis, apoptosis, immune response, and regulation of the tumor microenvironment. Therefore, it is considered a molecular target for prostate cancer treatment.
The role of PSA in prostate cancer
PSA is a recognized blood biomarker for prostate cancer recurrence. Serum PSA levels correlate with disease progression, but its diagnostic accuracy is controversial. PSA plays an important role in maintaining cancer cell growth and apoptosis. Its role in the tumor microenvironment is complex, and it can promote the development of prostate cancer by affecting cell proliferation, angiogenesis, and metastasis. PSA can stimulate the expression of tumor suppressor genes and participate in immune responses against tumor cells by activating cytotoxic T lymphocytes (CTLs). PSA can also be used as an imaging tool to help detect malignant areas and metastatic lesions within the prostate.
(Data source: Moradi A, et al. Cancer Metastasis Rev. 2019)
Clinical value of PSA
Tumor markers for prostate cancer: Under normal physiological conditions, PSA is primarily confined to prostate tissue, and serum PSA concentrations remain low, with a normal reference value of 0-4 ng/ml. However, when prostate tissue becomes cancerous, the cell structure is severely damaged, causing a significant increase in PSA concentrations in the blood. Therefore, PSA is considered the most valuable tumor marker for prostate cancer.
(Data source: Ibau C, et al. Biosens Bioelectron. 2017)
Targeted therapy: Development of targeted therapeutic drugs targeting PSA or its related signaling pathways, such as small molecule inhibitors targeting cell surface receptors or downstream signaling pathways activated by PSA.
Bispecific antibodies: Develop bispecific antibodies that can simultaneously bind to PSA and immune cells (such as T cells) to enhance the immune cells' ability to kill tumor cells.
Antibody-drug conjugates (ADCs): Develop antibodies targeting PSA and conjugate these antibodies with cytotoxic drugs to achieve precise targeting of prostate cancer cells.
