SLFN11 informs on standard of care and novel treatments in a wide range of cancer models.
Br J Cancer
; 124(5): 951-962, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33339894
ABSTRACT
BACKGROUND:
Schlafen 11 (SLFN11) has been linked with response to DNA-damaging agents (DDA) and PARP inhibitors. An in-depth understanding of several aspects of its role as a biomarker in cancer is missing, as is a comprehensive analysis of the clinical significance of SLFN11 as a predictive biomarker to DDA and/or DNA damage-response inhibitor (DDRi) therapies.METHODS:
We used a multidisciplinary effort combining specific immunohistochemistry, pharmacology tests, anticancer combination therapies and mechanistic studies to assess SLFN11 as a potential biomarker for stratification of patients treated with several DDA and/or DDRi in the preclinical and clinical setting.RESULTS:
SLFN11 protein associated with both preclinical and patient treatment response to DDA, but not to non-DDA or DDRi therapies, such as WEE1 inhibitor or olaparib in breast cancer. SLFN11-low/absent cancers were identified across different tumour types tested. Combinations of DDA with DDRi targeting the replication-stress response (ATR, CHK1 and WEE1) could re-sensitise SLFN11-absent/low cancer models to the DDA treatment and were effective in upper gastrointestinal and genitourinary malignancies.CONCLUSION:
SLFN11 informs on the standard of care chemotherapy based on DDA and the effect of selected combinations with ATR, WEE1 or CHK1 inhibitor in a wide range of cancer types and models.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Neoplasias da Mama
/
Proteínas Nucleares
/
Resistencia a Medicamentos Antineoplásicos
/
Inibidores de Proteínas Quinases
/
Padrão de Cuidado
/
Inibidores de Poli(ADP-Ribose) Polimerases
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido