Integrative Surface Antigen Profiling of KLK2 and STEAP1 in Advanced Prostate Cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• KLK2 and STEAP1 are cell surface targets relevant for prostate cancer treatment.
• Understanding their expression patterns in metastatic castration-resistant prostate cancer (mCRPC) is crucial for therapeutic development.

Purpose of the Study:

• To characterize the expression landscape of KLK2 and STEAP1 in mCRPC.
• To define associated transcriptomic, genomic, and epigenomic features.
• To inform the design of cell-surface antigen-directed therapies.

Main Methods:

• Analysis of 1095 patient samples from three mCRPC cohorts.
• In situ studies of rapid autopsy cases and patient-derived xenograft models.
• Transcriptomic, genomic, and epigenomic profiling.

Main Results:

• KLK2 and STEAP1 expression is enriched in AR-positive tumors, absent in neuroendocrine/double-negative phenotypes.
• Co-expression of KLK2, STEAP1, and PSMA suggests potential for co-targeting.
• Expression correlates with AR alterations and PSA levels, negatively with RB1/PTEN loss.
• Distinct regulatory mechanisms govern KLK2 (AR-dependent) and STEAP1 (partially AR-dependent, epigenetically regulated).
• Expression states associate with distinct transcriptional programs and immune microenvironments.

Conclusions:

• KLK2 and STEAP1 are key prostate adenocarcinoma-lineage antigens.
• Findings provide critical insights for rational design and clinical development of targeted therapies in prostate cancer.