Statin as anti-cancer therapy in autochthonous T-lymphomas expressing stabilized gain-of-function mutant p53 proteins
| Autor: | Laura Parrilla-Monge, Erica Di Cesare, Ute M. Moll, Karis Tutuska, Alice Nemajerova |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Statin Cancer therapy Lymphoma medicine.drug_class Immunology Mutant Article Cellular and Molecular Neuroscience In vivo medicine Humans Rosuvastatin Allele lcsh:QH573-671 Cancer models business.industry lcsh:Cytology Cell Biology medicine.disease In vitro Cancer research Mevalonate pathway Hydroxymethylglutaryl-CoA Reductase Inhibitors Tumor Suppressor Protein p53 business medicine.drug |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 11, Iss 4, Pp 1-12 (2020) |
| ISSN: | 2041-4889 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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