Lessons from tumor reversion for cancer treatment.
Curr Opin Oncol
; 25(1): 59-65, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-23165143
ABSTRACT
PURPOSE OF REVIEW Tumor reversion is the biological process by which highly tumorigenic cells lose at great extent or entirely their malignant phenotype. The purpose of our research is to understand the molecular program of tumor reversion and its clinical application. We first established biological models of reversion, which was done by deriving revertant cells from different tumors. Secondly, the molecular program that could override the malignant phenotype was assessed. Differential gene-expression profiling showed that at least 300 genes are implicated in this reversion process such as SIAH-1, PS1, TSAP6, and, most importantly, translationally controlled tumor protein (TPT1/TCTP). Decreasing TPT1/TCTP is key in reprogramming malignant cells, including cancer stem cells. RECENT FINDINGS:
Recent findings indicate that TPT1/TCTP regulates the P53-MDM2-Numb axis. Notably, TPT1/TCTP and p53 are implicated in a reciprocal negative-feedback loop. TPT1/TCTP is a highly significant prognostic factor in breast cancer. Sertraline and thioridazine interfere with this repressive feedback by targeting directly TPT1/TCTP and inhibiting its binding to MDM2, restoring wildtype p53 function. Combining sertraline with classical drugs such as Ara-C in acute myeloid leukemia may be also beneficial.SUMMARY:
In this review, we discuss some of these reversion pathways and how this approach could open a new route to cancer treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
/
Regulação Neoplásica da Expressão Gênica
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Proteína Supressora de Tumor p53
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Curr Opin Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
França