Investigators have found a key (dubbed “HULLK”) to the regulation of prostate cancer progression, which could in turn lead to the development of more effective therapies for patients with advanced disease (Mol Cancer. 2019;18[1]:113). Daniel Gioeli, PhD, Associate Professor of Microbiology, Immunology, and Cancer Biology, University of Virginia, spoke with Oncology Learning Network about the clinical significance of these findings.

What existing data led you and your co-investigators to conduct this research?

My lab performed a whole kinome screen for kinases that regulated prostate cancer growth. One of our hits from the screen did not express protein, leading to the hypothesis that there was a non-coding RNA within that kinase.

HULLK is a novel lncRNA situated within the LCK gene that may serve as an oncogene in prostate cancer. HULLK is dramatically upregulated by androgen in a dose-dependent manner, and the anti-androgen enzalutamide completely blocks this hormone-induced increase.

Therefore, we labeled this lncRNA “HULLK” for Hormone-Upregulated lncRNA within LCK. There is a significant positive correlation between HULLK expression and high-grade prostate cancer in multiple patient cohorts. shRNAs targeting HULLK significantly decreased prostate cancer cell growth.

Moreover, cells overexpressing HULLK were hypersensitive to androgen stimulation. The observation that HULLK expression increases in three independent cohorts indicate that the correlation with tumor grade is robust.

What are the possible real-world applications of these findings in clinical practice?

This discovery enhances our understanding of lncRNA and prostate cancer biology and may assist in the development of additional biomarkers or more effective therapeutic targets for advanced prostate cancer. More work, prospective clinical research, will be required to move this discovery into the clinic.

Do you and your co-investigators intend to expand upon this research?

Yes. I am currently working to uncover the mechanism of HULLK regulation of prostate cancer growth, to test the function of HULLK as a biomarker, and finally the applicability of inhibiting HULLK levels as a therapeutic approach.