Portal de investigación
Targeted Therapy Modulates the Secretome of Cancer-Associated Fibroblasts to Induce Resistance in HER2-Positive Breast Cancer.
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Luque, M
- Sanz-Alvarez, M
- Santamaria, A
- Zazo, S
- Cristobal, I
- de la Fuente, L
- Minguez, P
- Rovira, A
- Albanell, J
- Madoz-Gurpide, J
- Rojo, F
Grupos y Plataformas de I+D+i
Abstract
The combination of trastuzumab plus pertuzumab plus docetaxel as a first-line therapy in patients with HER2-positive metastatic breast cancer has provided significant clinical benefits compared to trastuzumab plus docetaxel alone. However, despite the therapeutic success of existing therapies targeting HER2, tumours invariably relapse. Therefore, there is an urgent need to improve our understanding of the mechanisms governing resistance, so that specific therapeutic strategies can be developed to provide improved efficacy. It is well known that the tumour microenvironment (TME) has a significant impact on cancer behaviour. Cancer-associated fibroblasts (CAFs) are essential components of the tumour stroma that have been linked to acquired therapeutic resistance and poor prognosis in breast cancer. For this reason, it would be of interest to identify novel biomarkers in the tumour stroma that could emerge as therapeutic targets for the modulation of resistant phenotypes. Conditioned medium experiments carried out in our laboratory with CAFs derived from HER2-positive patients showed a significant capacity to promote resistance to trastuzumab plus pertuzumab therapies in two HER2-positive breast cancer cell lines (BCCLs), even in the presence of docetaxel. In order to elucidate the components of the CAF-conditioned medium that may be relevant in the promotion of BCCL resistance, we implemented a multiomics strategy to identify cytokines, transcription factors, kinases and miRNAs in the secretome that have specific targets in cancer cells. The combination of cytokine arrays, label-free LC-MS/MS quantification and miRNA analysis to explore the secretome of CAFs under treatment conditions revealed several up- and downregulated candidates. We discuss the potential role of some of the most interesting candidates in generating resistance in HER2-positive breast cancer.
Datos de la publicación
- ISSN/ISSNe:
- 1661-6596, 1422-0067
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 34948097
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES MDPI AG
Citas Recibidas en Web of Science: 11
Documentos
Filiaciones
Keywords
- HER2-positive; breast cancer; cancer-associated fibroblast; label-free proteomics; miRNA; resistance; targeted therapy; trastuzumab; tumour microenvironment
Financiación
Proyectos y Estudios Clínicos
Caracterizacion y repercusion terapeutica de la ecologia de cancer de mama HER2 positivo
Investigador Principal: PILAR EROLES ASENSIO
PI18/01219 . INSTITUTO SALUD CARLOS III . 2019
Cita
Luque M,Sanz M,Santamaria A,Zazo S,Cristobal I,de la Fuente L,Minguez P,Eroles P,Rovira A,Albanell J,Madoz J,Rojo F. Targeted Therapy Modulates the Secretome of Cancer-Associated Fibroblasts to Induce Resistance in HER2-Positive Breast Cancer. Int. J. Mol. Sci. 2021. 22. (24):13297. IF:6,208. (1).
Targeted Therapy Modulates the Secretome of Cancer-Associated Fibroblasts to Induce Resistance in HER2-Positive Breast Cancer. Luque M, Sanz M, Santamaria A, Zazo S, Cristobal I, de la Fuente L, Minguez P et al. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2021 diciembre 10. 22 (24):DOI:10.3390/ijms222413297. PMID:34948097.
