The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response—Biological and Clinical Aspects
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. Nevert...
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doaj-f1a2dda9aa23471abb125c983da6f6ae2020-11-24T21:02:55ZengMDPI AGCancers2072-66942013-12-016112710.3390/cancers6010001cancers6010001The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response—Biological and Clinical AspectsMichaela Medová0Daniel M. Aebersold1Yitzhak Zimmer2Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, 3010 Bern, SwitzerlandDepartment of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, 3010 Bern, SwitzerlandDepartment of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, 3010 Bern, SwitzerlandRadiation 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.http://www.mdpi.com/2072-6694/6/1/1METDNA damage responseionizing radiationradiotherapyradioresistance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michaela Medová Daniel M. Aebersold Yitzhak Zimmer |
spellingShingle |
Michaela Medová Daniel M. Aebersold Yitzhak Zimmer The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response—Biological and Clinical Aspects Cancers MET DNA damage response ionizing radiation radiotherapy radioresistance |
author_facet |
Michaela Medová Daniel M. Aebersold Yitzhak Zimmer |
author_sort |
Michaela Medová |
title |
The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response—Biological and Clinical Aspects |
title_short |
The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response—Biological and Clinical Aspects |
title_full |
The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response—Biological and Clinical Aspects |
title_fullStr |
The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response—Biological and Clinical Aspects |
title_full_unstemmed |
The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response—Biological and Clinical Aspects |
title_sort |
molecular crosstalk between the met receptor tyrosine kinase and the dna damage response—biological and clinical aspects |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2013-12-01 |
description |
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. |
topic |
MET DNA damage response ionizing radiation radiotherapy radioresistance |
url |
http://www.mdpi.com/2072-6694/6/1/1 |
work_keys_str_mv |
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