US Pharm. 2019;44(8):5

With no treatment currently available, aggressive, metastatic-stage prostate cancer poses a major health challenge. A new research study, however, has uncovered a critical cellular mechanism that contributes to aggressive prostate cancer. The study was published in the journal Clinical Cancer Research.

The research, led by investigators at the Sidney Kimmel Cancer Center at Jefferson Health (SKCC) and their collaborators at Memorial Sloan Kettering Cancer Center, the University of California, San Francisco, and Celgene Corporation, focused on an enzyme called DNA-PK (DNA-dependent protein kinase), an important cellular component that controls DNA repair and influences gene expression. The work was headed by the laboratory of Karen E. Knudsen, PhD, executive vice president of oncology services and enterprise director of SKCC.

Earlier studies showed that DNA-PK is extremely active in metastatic prostate cancer and is associated with a poor prognosis. “Our study further elucidates the functions of DNA-PK and identifies this protein as a master regulator of gene networks that promote aggressive cancer behaviors,” says lead author Emanuela Dylgjeri.

A related study in the same issue, led by the laboratory of Felix Feng, MD, in collaboration with the Kundsen laboratory, linked DNA-PK to metastatic progression of the disease. To understand how DNA-PK causes poor outcomes, the investigators found that DNA-PK modulates the expression of gene networks controlling a variety of important cancer-related cellular processes, such as a developmental process called the epithelial-mesenchymal transition, the immune response, and metabolic pathways.

The findings suggest that targeting DNA-PK might allow the development of effective strategies to prevent or treat aggressive, late-stage prostate cancer. Data from the studies were used to develop a clinical trial combining standard-of-care with a first-in-man DNA-PK inhibitor. Early results of the trial have been encouraging: The researchers have shown in a laboratory setting that the combined approach is more effective than either single treatment in eliciting antitumor effects. Now in the testing expansion stage, the clinical trial is still underway.

The newly published studies focus on translating basic science findings from the laboratory to the clinic. The investigators, however, also plan to take the lessons learned in the clinic back to the laboratory. The results of the clinical trial should offer important clues and guide the design of new experiments, ultimately broadening the understanding of how DNA-PK regulates specific cellular pathways to promote aggressive prostate cancer.

For a look at another, albeit less serious, disease of the prostate, see “A Community Pharmacist Role in the Treatment of Bacterial Prostatitis,” by Ashley Barlow, PharmD, Brooke Barlow, PharmD, and Jason C. Gallagher, PharmD, FCCP, FIDP, FIDSA, BCPS (this issue, page 24).

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