Targeting the ATR-CHK1 Axis in Cancer Therapy
Targeting the DNA damage response (DDR) is a new therapeutic approach in cancer that shows great promise for tumour selectivity. Key components of the DDR are the ataxia telangiectasia mutated and Rad3 related (ATR) and checkpoint kinase 1 (CHK1) kinases. This review article describes the role of ATR and its major downstream target, CHK1, in the DDR and why cancer cells are particularly reliant on the ATR-CHK1 pathway, providing the rationale for targeting these kinases, and validation of this hypothesis by genetic manipulation. The recent development of specific inhibitors and preclinical data using these inhibitors not only as chemosensitisers and radiosensitisers but also as single agents to exploit specific pathologies of tumour cells is described. These potent and specific inhibitors have now entered clinical trial and early results are presented.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2017 |
---|---|
Erschienen: |
2017 |
Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
---|---|
Enthalten in: |
Cancers - 9(2017), 5 vom: 27. Apr. |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Rundle, Stuart [VerfasserIn] |
---|
Links: |
---|
Themen: |
ATR |
---|
Anmerkungen: |
Date Revised 09.01.2021 published: Electronic Citation Status PubMed-not-MEDLINE |
---|
doi: |
10.3390/cancers9050041 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM271345055 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM271345055 | ||
003 | DE-627 | ||
005 | 20231224232515.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231224s2017 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3390/cancers9050041 |2 doi | |
028 | 5 | 2 | |a pubmed24n0904.xml |
035 | |a (DE-627)NLM271345055 | ||
035 | |a (NLM)28448462 | ||
035 | |a (PII)E41 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Rundle, Stuart |e verfasserin |4 aut | |
245 | 1 | 0 | |a Targeting the ATR-CHK1 Axis in Cancer Therapy |
264 | 1 | |c 2017 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Revised 09.01.2021 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status PubMed-not-MEDLINE | ||
520 | |a Targeting the DNA damage response (DDR) is a new therapeutic approach in cancer that shows great promise for tumour selectivity. Key components of the DDR are the ataxia telangiectasia mutated and Rad3 related (ATR) and checkpoint kinase 1 (CHK1) kinases. This review article describes the role of ATR and its major downstream target, CHK1, in the DDR and why cancer cells are particularly reliant on the ATR-CHK1 pathway, providing the rationale for targeting these kinases, and validation of this hypothesis by genetic manipulation. The recent development of specific inhibitors and preclinical data using these inhibitors not only as chemosensitisers and radiosensitisers but also as single agents to exploit specific pathologies of tumour cells is described. These potent and specific inhibitors have now entered clinical trial and early results are presented | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Review | |
650 | 4 | |a ATR | |
650 | 4 | |a CHK1 | |
650 | 4 | |a DNA-damage | |
650 | 4 | |a DNA-repair | |
650 | 4 | |a cell cycle | |
650 | 4 | |a chemotherapy-sensitising-agents | |
650 | 4 | |a protein-kinase-inhibitors | |
650 | 4 | |a radiation-sensitising-agents | |
700 | 1 | |a Bradbury, Alice |e verfasserin |4 aut | |
700 | 1 | |a Drew, Yvette |e verfasserin |4 aut | |
700 | 1 | |a Curtin, Nicola J |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Cancers |d 2009 |g 9(2017), 5 vom: 27. Apr. |w (DE-627)NLM198667213 |x 2072-6694 |7 nnns |
773 | 1 | 8 | |g volume:9 |g year:2017 |g number:5 |g day:27 |g month:04 |
856 | 4 | 0 | |u http://dx.doi.org/10.3390/cancers9050041 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 9 |j 2017 |e 5 |b 27 |c 04 |