MRE11 as a molecular signature and therapeutic target for cancer treatment with radiotherapy. (28th August 2021)

• Record Type: Journal Article
• Authors: Wang, Yen-Yun; Hung, Amos C.; Lo, Steven; Hsieh, Ya-Ching; Yuan, Shyng-Shiou F.
• Is Part Of: Cancer letters. Volume 514(2021)
• Page Start: 1
• Page End: 11
• Publication Date: 2021-08-28
• Subjects: DNA repair -- Ionizing radiation -- MRE11 -- Radioresistance -- Radiotherapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2021.05.013
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: MRE11, the core of the MRE11/RAD50/NBS1 complex, is one of key DNA damage response proteins. Increasing evidence suggests that its expression in cancer cells is critical to developing radioresistance; as such, MRE11 is an emerging marker for targeted radiosensitization strategies. Elevated MRE11 in tumor tissues has been associated with poor survival in patients undergoing radiotherapy, although in some cancer types, the opposite has been noted. The recent discovery of ionizing radiation-induced truncation of MRE11, which decreases its efficacy, may explain some of these paradoxical findings. The progress of research on the biological modulation of MRE11 expression is also discussed, with the potential application of small molecule or large molecule inhibitors of MRE11 for enhancing radiosensitivity. Current research has further highlighted both nuclease and non-nuclease activities of MRE11 in cancer cells treated with ionizing radiation, and differentiation between these is essential to verify the targeting effects of radiosensitizing agents. These updates clarify our understanding of how MRE11 expression may be utilized in future stratification of cancer patients for radiotherapy, and how it may be leveraged in shaping novel radiosensitization strategies. Highlights: Elevated MRE11 expression adversely affects patient outcomes following radiotherapy. Paradoxical data exist between MRE11 expression and radiotherapeutic outcomes. Truncated MRE11 with impaired activity may partly explain these paradoxical findings. Nuclease-dependent function of MRE11 emerges as a novel radiosensitization target. Leveraging MRE11 expression may enhance the therapeutic efficacy of radiotherapy.