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Cancers 2014, 6(1), 1-27; doi:10.3390/cancers6010001
Review

The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response—Biological and Clinical Aspects

1,2,* , 1,2
 and 1,2,*
Received: 1 October 2013; in revised form: 6 December 2013 / Accepted: 6 December 2013 / Published: 19 December 2013
(This article belongs to the Special Issue MET in Cancer)
View Full-Text   |   Download PDF [656 KB, uploaded 19 December 2013]
Abstract: Radiation therapy remains an imperative treatment modality for numerous malignancies. Enduring significant technical achievements both on the levels of treatment planning and radiation delivery have led to improvements in local control of tumor growth and reduction in healthy tissue toxicity. Nevertheless, resistance mechanisms, which presumably also involve activation of DNA damage response signaling pathways that eventually may account for loco-regional relapse and consequent tumor progression, still remain a critical problem. Accumulating data suggest that signaling via growth factor receptor tyrosine kinases, which are aberrantly expressed in many tumors, may interfere with the cytotoxic impact of ionizing radiation via the direct activation of the DNA damage response, leading eventually to so-called tumor radioresistance. The aim of this review is to overview the current known data that support a molecular crosstalk between the hepatocyte growth factor receptor tyrosine kinase MET and the DNA damage response. Apart of extending well established concepts over MET biology beyond its function as a growth factor receptor, these observations directly relate to the role of its aberrant activity in resistance to DNA damaging agents, such as ionizing radiation, which are routinely used in cancer therapy and advocate tumor sensitization towards DNA damaging agents in combination with MET targeting.
Keywords: MET; DNA damage response; ionizing radiation; radiotherapy; radioresistance MET; DNA damage response; ionizing radiation; radiotherapy; radioresistance
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Medová, M.; Aebersold, D.M.; Zimmer, Y. The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response—Biological and Clinical Aspects. Cancers 2014, 6, 1-27.

AMA Style

Medová M, Aebersold DM, Zimmer Y. The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response—Biological and Clinical Aspects. Cancers. 2014; 6(1):1-27.

Chicago/Turabian Style

Medová, Michaela; Aebersold, Daniel M.; Zimmer, Yitzhak. 2014. "The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response—Biological and Clinical Aspects." Cancers 6, no. 1: 1-27.



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