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Resistance mechanis...
Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy : can we overcome them?
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- Haronikova, Lucia (författare)
- RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
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- Bonczek, Ondrej (författare)
- Umeå universitet,Patologi,RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
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- Zatloukalova, Pavlina (författare)
- RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
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- Kokas-Zavadil, Filip (författare)
- RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
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- Kucerikova, Martina (författare)
- RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, Brno, Czech Republic
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- Coates, Philip J. (författare)
- RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
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- Fåhraeus, Robin (författare)
- Umeå universitet,Patologi,RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic; Inserm UMRS1131, Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, Paris, France
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- Vojtesek, Borivoj (författare)
- RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
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(creator_code:org_t)
- 2021-12-15
- 2021
- Engelska.
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Ingår i: Cellular & Molecular Biology Letters (Druk). - : BioMed Central. - 1425-8153 .- 1689-1392. ; 26:1
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://cmbl.biomedc...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Since the discovery of the first MDM2 inhibitors, we have gained deeper insights into the cellular roles of MDM2 and p53. In this review, we focus on MDM2 inhibitors that bind to the p53-binding domain of MDM2 and aim to disrupt the binding of MDM2 to p53. We describe the basic mechanism of action of these MDM2 inhibitors, such as nutlin-3a, summarise the determinants of sensitivity to MDM2 inhibition from p53-dependent and p53-independent points of view and discuss the problems with innate and acquired resistance to MDM2 inhibition. Despite progress in MDM2 inhibitor design and ongoing clinical trials, their broad use in cancer treatment is not fulfilling expectations in heterogenous human cancers. We assess the MDM2 inhibitor types in clinical trials and provide an overview of possible sources of resistance to MDM2 inhibition, underlining the need for patient stratification based on these aspects to gain better clinical responses, including the use of combination therapies for personalised medicine.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Combination therapy
- MDM2
- MDM2 inhibitor
- Nutlin-3a
- p53
- Personalised medicine
- Resistance
Publikations- och innehållstyp
- ref (ämneskategori)
- for (ämneskategori)
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