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Radiosensitization of renal cell carcinoma in vitro through the induction of autophagy

Ferguson, David J.P.; Anbalagan, Selvakumar; Monteiro dos Santos Pires, Isabel; Blick, Christopher; Hill, Mark A.; Ferguson, David J. P.; Chan, Denise A.; Hammond, Ester M.

Authors

David J.P. Ferguson

Selvakumar Anbalagan

Christopher Blick

Mark A. Hill

David J. P. Ferguson

Denise A. Chan

Ester M. Hammond

Abstract

Background and purpose: For patients diagnosed with advanced renal cell carcinoma (RCC), there are few therapeutic options. Radiation therapy is predominantly used to treat metastasis and has not proven effective in the adjuvant setting for renal cancer. Furthermore, RCC is resistant to standard cytotoxic chemotherapies. Targeted anti-angiogenics are the standard of care for RCC but are not curative. Newer agents, such as mTOR inhibitors and others that induce autophagy, have shown great promise for treating RCC. Here, we investigate the potential use of the small molecule STF-62247 to modulate radiation. Materials and methods: Using RCC cell lines, we evaluate sensitivity to radiation in addition to agents that induce autophagic cell death by clonogenic survival assays. Furthermore, these were also tested under physiological oxygen levels. Results: STF-62247 specifically induces autophagic cell death in cells that have lost VHL, an essential mutation in the development of RCC. Treatment with STF-62247 did not alter cell cycle progression but when combined with radiation increased cell killing under oxic and hypoxic/physiological conditions. Conclusions: This study highli ghts the possibility of combining targeted therapeutics such as STF-62247 or temsirolimus with radiation to reduce the reliance on partial or full nephrectomy and improve patient prognosis. © 2012 Elsevier Ireland Ltd. All rights reserved.

Journal Article Type Article
Publication Date Jun 1, 2012
Journal RADIOTHERAPY AND ONCOLOGY
Print ISSN 0167-8140
Electronic ISSN 1879-0887
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 103
Issue 3
Pages 388-393
Institution Citation Anbalagan, S., Monteiro dos Santos Pires, I., Blick, C., Hill, M. A., Ferguson, D. J. P., Chan, D. A., & Hammond, E. M. (2012). Radiosensitization of renal cell carcinoma in vitro through the induction of autophagy. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 103(3), (388-393). doi:10.1016/j.radonc.2012.04.001. ISSN 0167-8140
DOI https://doi.org/10.1016/j.radonc.2012.04.001
Keywords Autophagy; Radiation; VHL; Radiosensitivity; Hypoxia
Publisher URL https://www.sciencedirect.com/science/article/pii/S0167814012001570?via%3Dihub