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Statin as anti-cancer therapy in autochthonous T-lymphomas expressing stabilized gain-of-function mutant p53 proteins

Tutuska, Karis, Parrilla-Monge, Laura, Di Cesare, Erica, Nemajerova, Alice, Moll, Ute M.·2020·Cell Death & Disease
DOI 10.1038/s41419-020-2466-4
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Abstract

An important component of missense mutant p53 gain-of-function (mutp53 GOF) activities is the ability of stabilized mutp53 proteins to upregulate the mevalonate pathway, providing a rationale for exploring the statin family of HMG-CoA reductase inhibitors as anticancer agents in mutp53 tumors. In this small exploratory study we report on the effects of statin treatment in autochthonous mouse models of clinically advanced T-cell lymphoma expressing two different GOF mutp53 alleles. We find that Rosuvastatin monotherapy shows a modest, p53 allele-selective and transient anti-tumor effect in autochthonous T-lymphomas expressing the p53 R248Q DNA contact mutant, but not in tumors expressing the p53 R172H conformational mutant. p53 null mice also do not benefit. In vitro statin sensitivity is not a strong predictor for in vivo sensitivity, while subcutaneous allografts are. Future explorations of statins in combination therapies are justified to improve its anti-tumor effects and to better define the most statin-sensitive alleles and tumor types among mutp53-stabilized cancers.

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Metadata

Authors
Tutuska, K., Parrilla-Monge, L., Di Cesare, E., Nemajerova, A., & Moll, U. M.
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2020-04-24
Volume
11
Issue
4
ISSN
2041-4889
DOI
10.1038/s41419-020-2466-4
Cited by
20
References
0
Language
en
Licence
Funders
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute (2RO1CA176647)
  • Stony Brook Foundation

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CoChat. (2026). Citation check: Statin as anti-cancer therapy in autochthonous T-lymphomas expressing stabilized gain-of-function mutant p53 proteins. https://app.cochat.ai/papers/10.1038/s41419-020-2466-4
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Tutuska, K., Parrilla-Monge, L., Di Cesare, E., Nemajerova, A., & Moll, U. M. (2020). Statin as anti-cancer therapy in autochthonous T-lymphomas expressing stabilized gain-of-function mutant p53 proteins. Cell Death & Disease. https://doi.org/10.1038/s41419-020-2466-4

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