Pleiotropic Impact of DNA-PK in Cancer and Implications for Therapeutic Strategies.
Publication/Presentation Date
9-15-2019
Abstract
PURPOSE: DNA-dependent protein kinase catalytic subunit (DNA-PK) is a pleiotropic kinase involved in DNA repair and transcriptional regulation. DNA-PK is deregulated in selected cancer types and is strongly associated with poor outcome. The underlying mechanisms by which DNA-PK promotes aggressive tumor phenotypes are not well understood. Here, unbiased molecular investigation in clinically relevant tumor models reveals novel functions of DNA-PK in cancer.
RESULTS: Key findings reveal that (i) DNA-PK regulates tumor cell proliferation; (ii) pharmacologic targeting of DNA-PK suppresses tumor growth both
CONCLUSIONS: These findings uncovered novel DNA-PK transcriptional regulatory functions and led to the development of a combinatorial therapeutic strategy for patients with advanced prostate cancer, currently being tested in the clinical setting.
Volume
25
Issue
18
First Page
5623
Last Page
5637
ISSN
1557-3265
Published In/Presented At
Dylgjeri, E., McNair, C., Goodwin, J. F., Raymon, H. K., McCue, P. A., Shafi, A. A., Leiby, B. E., de Leeuw, R., Kothari, V., McCann, J. J., Mandigo, A. C., Chand, S. N., Schiewer, M. J., Brand, L. J., Vasilevskaya, I., Gordon, N., Laufer, T. S., Gomella, L. G., Lallas, C. D., Trabulsi, E. J., … Knudsen, K. E. (2019). Pleiotropic Impact of DNA-PK in Cancer and Implications for Therapeutic Strategies. Clinical cancer research : an official journal of the American Association for Cancer Research, 25(18), 5623–5637. https://doi.org/10.1158/1078-0432.CCR-18-2207
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
31266833
Department(s)
Administration and Leadership
Document Type
Article