KLK2 (Kallikrein-related peptidase 2)

Nonetheless, challenges remain around long-term hematologic and renal safety, radionuclide supply, protocol standardization, and global accessibility. Ongoing and future multicenter trials, collaborative consortia, and innovations in theranostics will be critical to defining optimal patient selection, sequencing with existing therapies, and embedding RLT as a key pillar in the management of advanced PCa.

By inhibition with the recombinant protease inhibitor MDPK67b targeting KLK2 and other trypsin-like KLKs including KLK4 and KLK14, we investigated the antitumor response and the influence on AR downstream target genes with MDPK67b in PCa cell lines in vitro...Therefore, inhibition of KLKs represents a promising and AR-independent approach to treat advanced and CRPCa. ClinicalTrials.gov ID: NCT04644770.

Our findings make α2δ1 protein a novel and promising diagnostic biomarker to differentiate PC from BPH.

Prior to the advent of ICIs, prostate cancer had one of the first approvals for cancer immunotherapy with sipleucel-T, an anti-cancer vaccine...Most notably, clinical trials with bispecific T-cell engagers (BiTEs) targeting tumor antigens like STEAP-1 and KLK2 have shown clinical promise. Moving beyond ICIs may lead to new approaches to alter the prostate cancer tumor immune microenvironment and improve clinical outcomes.

KLK2 was not previously recognized as a therapeutic target as it is secreted. It has now been demonstrated that KLK2 is expressed on the cell surface and targetable by various methodologies.

Altogether, our analysis indicates a suboptimal design of several cancer vaccines currently in clinical development: ATP128, BNT111, BNT112, BNT116, INO-5401. We recommend that next-generation cancer vaccines should integrate rigorous epitope filtering strategies to eliminate shared sequences in TAAs.

Our study establishes KLK2 as a highly prostate-specific cell surface target. Targeting KLK2 with various MoA represents novel therapeutic approaches for advanced PCa.

Pasritamig demonstrated a favorable safety profile with very low rates of CRS and could be safely administered in an outpatient setting. Preliminary antitumor activity demonstrated proof of concept for KLK2 as a target in PC, warranting further development of pasritamig.

Further testing confirmed effective cytotoxic killing potential of KLK4-A2 TCR in vitro and in vivo, underscoring its therapeutic potential. These findings highlight the promise of the KLK4-A2 TCR for prostate cancer immunotherapy and demonstrate that prostate-specific antigens can be effectively targeted using TCR-gene transfer strategies.

While experimental validation of enzymatic inhibition and antitumor efficacy is required, this study provides a structural and mechanistic foundation for advancing these candidates into preclinical testing. These results also highlight the use of phytochemical libraries and dynamics-driven virtual screening in developing targeted therapies for prostate cancer.

Overall, our data show that the variety of responses to ceramide of the same cell type is dependent on the concentration used. Low doses do not affect sphingolipid metabolism, and high doses do so with a different cellular response.

Functional analysis indicated significant differences in dysfunction patterns between risk groups. This study identified five mitochondrial autophagy-related prognostic genes and constructed a risk model, offering novel insights into OS diagnosis and therapeutic strategies.