A promising drug target gaining attention is Polynucleotide Kinase/Phosphatase (PNKP), a key player in DNA repair mechanisms within our cells.

PNKP is an enzyme that repairs damaged DNA, ensuring cell survival and genetic stability. While this function is vital for healthy cells, it also aids cancer cells in resisting treatments like radiation and chemotherapy by fixing therapy-induced DNA damage.

In prostate cancer, especially in advanced stages, cancer cells often develop resistance to conventional therapies. Research indicates that inhibiting PNKP can sensitize these cells to treatment, making them more susceptible to DNA damage-induced cell death.

PNKP interacts with key DNA repair pathways involving ATM and BRCA, proteins that are often mutated in advanced prostate cancer. Targeting PNKP in tumors with these mutations may amplify the effects of DNA-damaging therapies, offering a new therapeutic angle.

A new PNKP inhibitor is scheduled to begin Phase 1 clinical trials in 2025, marking the first step in assessing its safety and effectiveness in humans. While the initial focus may include different cancer types, the implications for prostate cancer are significant, given PNKP’s role in DNA repair and treatment resistance.

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