Resistance mechanisms to inhibitors of p53-MDM2 interactions in
cancer therapy: can we overcome them?

J 2021

Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?

HÁRONÍKOVÁ, Lucia, Ondřej BONCZEK, Pavlína ZATLOUKALOVÁ, Filip KOKÁŠ-ZAVADIL, Martina KUČERÍKOVÁ et. al.

Základní údaje

Originální název

Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?

Autoři

HÁRONÍKOVÁ, Lucia, Ondřej BONCZEK, Pavlína ZATLOUKALOVÁ, Filip KOKÁŠ-ZAVADIL, Martina KUČERÍKOVÁ (703 Slovensko, domácí), Philip J. COATES, Robin FAHRAEUS a Bořivoj VOJTĚŠEK (garant)

Vydání

Cellular & Molecular Biology Letters, BMC, 2021, 1425-8153

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 8.702

Kód RIV

RIV/00216224:14310/21:00123475

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1186/s11658-021-00293-6

UT WoS

000730550700001

Klíčová slova anglicky

p53; MDM2; MDM2 inhibitor; Nutlin-3a; Resistance; Combination therapy; Personalised medicine

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 21. 4. 2022 10:35, Mgr. Marie Šípková, DiS.

Anotace

V originále

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.

Citovat

HÁRONÍKOVÁ, Lucia, Ondřej BONCZEK, Pavlína ZATLOUKALOVÁ, Filip KOKÁŠ-ZAVADIL, Martina KUČERÍKOVÁ, Philip J. COATES, Robin FAHRAEUS a Bořivoj VOJTĚŠEK. Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them? Cellular & Molecular Biology Letters. BMC, 2021, roč. 26, č. 1, s. 1-33. ISSN 1425-8153. Dostupné z: https://dx.doi.org/10.1186/s11658-021-00293-6.

@article{1816287,
   author = {Hároníková, Lucia and Bonczek, Ondřej and Zatloukalová, Pavlína and KokášandZavadil, Filip and Kučeríková, Martina and Coates, Philip J. and Fahraeus, Robin and Vojtěšek, Bořivoj},
   article_number = {1},
   doi = {http://dx.doi.org/10.1186/s11658-021-00293-6},
   keywords = {p53; MDM2; MDM2 inhibitor; Nutlin-3a; Resistance; Combination therapy; Personalised medicine},
   language = {eng},
   issn = {1425-8153},
   journal = {Cellular & Molecular Biology Letters},
   title = {Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?},
   url = {https://cmbl.biomedcentral.com/articles/10.1186/s11658-021-00293-6},
   volume = {26},
   year = {2021}
}

TY  - JOUR
ID  - 1816287
AU  - Hároníková, Lucia - Bonczek, Ondřej - Zatloukalová, Pavlína - Kokáš-Zavadil, Filip - Kučeríková, Martina - Coates, Philip J. - Fahraeus, Robin - Vojtěšek, Bořivoj
PY  - 2021
TI  - Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?
JF  - Cellular & Molecular Biology Letters
VL  - 26
IS  - 1
SP  - 1-33
EP  - 1-33
PB  - BMC
SN  - 14258153
KW  - p53
KW  - MDM2
KW  - MDM2 inhibitor
KW  - Nutlin-3a
KW  - Resistance
KW  - Combination therapy
KW  - Personalised medicine
UR  - https://cmbl.biomedcentral.com/articles/10.1186/s11658-021-00293-6
N2  - 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.
ER  -

HÁRONÍKOVÁ, Lucia, Ondřej BONCZEK, Pavlína ZATLOUKALOVÁ, Filip KOKÁŠ-ZAVADIL, Martina KUČERÍKOVÁ, Philip J. COATES, Robin FAHRAEUS a Bořivoj VOJTĚŠEK. Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them? \textit{Cellular \&{} Molecular Biology Letters}. BMC, 2021, roč.~26, č.~1, s.~1-33. ISSN~1425-8153. Dostupné z: https://dx.doi.org/10.1186/s11658-021-00293-6.

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