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The prognostic value of MEK pathway-associated estrogen receptor signaling activity for female cancers.
Ng, Chun Wai; Tsang, Yvonne T M; Gershenson, David M; Wong, Kwong-Kwok.
Afiliación
  • Ng CW; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Tsang YTM; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Gershenson DM; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wong KK; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. kkwong@mdanderson.org.
Br J Cancer ; 130(11): 1875-1884, 2024 May.
Article en En | MEDLINE | ID: mdl-38582811
ABSTRACT

BACKGROUND:

Other than for breast cancer, endocrine therapy has not been highly effective for gynecologic cancers. Endocrine therapy resistance in estrogen receptor positive gynecologic cancers is still poorly understood. In this retrospective study, we examined the estrogen receptor (ER) signaling pathway activities of breast, ovarian, endometrial, and cervical cancers to identify those that may predict endocrine therapy responsiveness.

METHODS:

Clinical and genomic data of women with breast and gynecological cancers were downloaded from cBioPortal for Cancer Genomics. Estrogen receptor alpha (ESR1) expression level and sample-level pathway enrichment scores (EERES) were calculated to classify patients into four groups (low/high ESR1 and low/high EERES). Correlation between ESR1/EERES score and survival was further validated with RNAseq data from low-grade serous ovarian cancer. Pathway analyses were performed among different ESR1/EERES groups to identify genes that correlate with endocrine resistance, which are validated using Cancer Cell Line Encyclopedia gene expression and Genomics of Drug Sensitivity in Cancer data.

RESULTS:

We identified a novel combined prognostic value of ESR1 expression and the corresponding estrogen response signaling (EERES score) for breast cancer. The combined prognostic value (ESR1/EERES) may be applicable to other gynecologic cancers. More importantly, we discovered that ER signaling can cross-regulate MEK pathway activation. We identified downstream genes in the MEK pathway (EPHA2, INAVA, MALL, MPZL2, PCDH1, and TNFRSF21) that are potential endocrine therapy response biomarkers.

CONCLUSION:

This study demonstrated that targeting both the ER and the ER signaling activity related MEK pathway may aid the development of endocrine therapy strategies for personalized medicine.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptor alfa de Estrógeno Límite: Female / Humans Idioma: En Revista: Br J Cancer Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptor alfa de Estrógeno Límite: Female / Humans Idioma: En Revista: Br J Cancer Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido