Idioma:

A gene expression signature of retinoblastoma loss-of-function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer

Malorni, Luca ; Piazza, Silvano ; Ciani, Yari ; Guarducci, Cristina ; Bonechi, Martina ; Biagioni, Chiara ; Hart, Christopher D ; Verardo, Roberto ; Di Leo, Angelo ; Migliaccio, Ilenia

Oncotarget, 2016-09, Vol.7 (42), p.68012-68022

United States: Impact Journals LLC

Texto completo disponível

Citações Citado por

Enviar para

Título:
A gene expression signature of retinoblastoma loss-of-function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer
Autor: Malorni, Luca ; Piazza, Silvano ; Ciani, Yari ; Guarducci, Cristina ; Bonechi, Martina ; Biagioni, Chiara ; Hart, Christopher D ; Verardo, Roberto ; Di Leo, Angelo ; Migliaccio, Ilenia
Assuntos: Antineoplastic Agents - therapeutic use ; Biomarkers - metabolism ; Biomarkers, Pharmacological - metabolism ; Breast Neoplasms - diagnosis ; Breast Neoplasms - genetics ; Breast Neoplasms - mortality ; Cell Line, Tumor ; Cyclin-Dependent Kinase 4 - antagonists & inhibitors ; Cyclin-Dependent Kinase 6 - antagonists & inhibitors ; Datasets as Topic ; Drug Resistance, Neoplasm ; E2F1 Transcription Factor - genetics ; E2F1 Transcription Factor - metabolism ; E2F2 Transcription Factor - genetics ; E2F2 Transcription Factor - metabolism ; Female ; Humans ; Mutation - genetics ; Piperazines - therapeutic use ; Prognosis ; Pyridines - therapeutic use ; Receptor, ErbB-2 - metabolism ; Receptors, Estrogen - metabolism ; Research Paper ; Retinoblastoma Protein - genetics ; Retinoblastoma Protein - metabolism ; Survival Analysis ; Transcriptome
É parte de: Oncotarget, 2016-09, Vol.7 (42), p.68012-68022
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: Palbociclib is a CDK4/6 inhibitor that received FDA approval for treatment of hormone receptor positive (HR+) HER2 negative (HER2neg) advanced breast cancer. To better personalize patients treatment it is critical to identify subgroups that would mostly benefit from it. We hypothesize that complex alterations of the Retinoblastoma (Rb) pathway might be implicated in resistance to CDK4/6 inhibitors and aim to investigate whether signatures of Rb loss-of-function would identify breast cancer cell lines resistant to palbociclib. We established a gene expression signature of Rb loss-of-function (RBsig) by identifying genes correlated with E2F1 and E2F2 expression in breast cancers within The Cancer Genome Atlas. We assessed the RBsig prognostic role in the METABRIC and in a comprehensive breast cancer meta-dataset. Finally, we analyzed whether RBsig would discriminate palbociclib-sensitive and -resistant breast cancer cells in a large RNA sequencing-based dataset. The RBsig was associated with RB1 genetic status in all tumors (p <7e-32) and in luminal or basal subtypes (p < 7e-11 and p < 0.002, respectively). The RBsig was prognostic in the METABRIC dataset (discovery: HR = 1.93 [1.5-2.4] p = 1.4e-08; validation: HR = 2.01 [1.6-2.5] p = 1.3e-09). Untreated and endocrine treated patients with estrogen receptor positive breast cancer expressing high RBsig had significantly worse recurrence free survival compared to those with low RBsig (HR = 2.37 [1.8 - 3.2] p = 1.87e-08 and HR = 2.62 [1.9- 3.5] p = 8.6e-11, respectively). The RBsig was able to identify palbociclib resistant and sensitive breast cancer cells (ROC AUC = 0,7778). Signatures of RB loss might be helpful in personalizing treatment of patients with HR+/HER2neg breast cancer. Further validation in patients receiving palbociclib is warranted.
Editor: United States: Impact Journals LLC
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

A gene expression signature of retinoblastoma loss-of-function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer

Malorni, Luca ; Piazza, Silvano ; Ciani, Yari ; Guarducci, Cristina ; Bonechi, Martina ; Biagioni, Chiara ; Hart, Christopher D ; Verardo, Roberto ; Di Leo, Angelo ; Migliaccio, Ilenia

United States: Impact Journals LLC

Buscando em bases de dados remotas. Favor aguardar.