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Deciphering the Role of aberrant glycOSylation in the rEsponse to Targeted TherA...

Deciphering the Role of aberrant glycOSylation in the rEsponse to Targeted TherApies for breast cancer Resistance and cancer progression remain a major obstacle to the successful treatment of cancer. In HER2+ breast cancer, the development of targeted therapies such as trastuzumab, has revolutionized the treatment for these cancer... ver más

21/07/2022

ERASMUS MC

176K€

Presupuesto del proyecto: 176K€

Líder del proyecto

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDA... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2022-07-21

MSCA-IF-2019: Individual Fellowships

I+D

Cerrada hace 5 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

ERASMUS MC

175.57K€ | Lider

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Duración del proyecto: 28 meses Fecha Inicio: 2020-03-18
Fecha Fin: 2022-07-21

Líder del proyecto

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDA... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 176K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Resistance and cancer progression remain a major obstacle to the successful treatment of cancer. In HER2+ breast cancer, the development of targeted therapies such as trastuzumab, has revolutionized the treatment for these cancer patients. However, a significant number of patients develop resistance. In this realm, my previous work focused on understanding the crosstalk of interconnected signaling pathways in HER2+ cancer cells that drive tumorigenesis and undermine the efficacy of current treatments. The research goal of this proposal is to provide a new focus to the challenge of resistance by deciphering the role of glycosylation in driving resistance to HER2-targeted therapies. Aberrant glycosylation of proteins is a hallmark in cancer and has been linked to multiple processes such as invasion, angiogenesis and modulation of the immune response. The receptor HER2, the main driver of HER2+ cancers, is heavily glycosylated and is the target of current antibody-based treatments, including trastuzumab. In this scenario, this proposal aims to (1) identify glycosylation-related genes associated with incomplete pathological response to trastuzumab to (2) dissect their role on trastuzumab binding and (3) assess their impact in the response to trastuzumab mediated by immune cells. This research plan will be accomplished combining the analysis of clinical data from tumor biopsies, the use of trastuzumab-resistant tumor-derived breast cancer cell lines and, the implementation and imaging of 3D heterotypic cultures of cancer cell line-derived spheroids and immune cells. Thus, this proposal addresses a largely unexplored layer of complexity in cancer biology – the role of glycosylation in resistance to targeted therapies – and holds the potential to identify new markers of response to therapies and open the path to new therapeutic options for the improvement of current treatments.

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