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Insertional mutagenesis to identify molecular mechanisms of breast cancer dormancy and metastasis

Project description

Insight into the mechanism of metastasis

Cancer is a multifactorial disease with the tumour microenvironment and cell-intrinsic processes impacting disease progression and metastasis. Over the years, omics technologies have contributed to the molecular characterisation of many types of cancer. However, the mechanisms and determinant factors responsible for metastases formation are incompletely understood. PB_dormancy, a project funded by the EU, will investigate the molecular mechanisms that control breast cancer dormancy and metastasis. Scientists will use an insertional mutagenesis screening approach to identify genetic loci implicated in metastasis onset. The project has the potential to unveil new therapeutic targets against breast cancers with high risk for recurrence and poor prognosis.

Objective

Metastatic disease is the leading cause of cancer deaths, yet our understanding of this process and therapeutic choices are extremely limited. The recent explosive development of high-throughput technologies in genomics and proteomics has begun to unravel the complexity of cancer biology, highlighting the need to approach the study of cancer from a systems biology perspective. Results of recent studies have underscored the crucial roles of the tumor microenvironment as well as cell-intrinsic processes, such as autophagy, in cancer cell survival and dissemination. These surviving cells may lay dormant or be triggered to proliferate and establish active metastatic lesions after a variable period of time. I propose an innovative project in which I will exploit the unique opportunity to dissect molecular mechanisms controlling breast cancer dormancy and metastasis employing cutting-edge technologies in the field of functional genomics. This technology includes several state-of-the-art technical advances in the fields of in vitro and in vivo modeling of tumor cell dormancy, functional forward genomics using the PiggyBac transposon-based system for insertional mutagenesis screens, next generation sequencing, advanced bioinformatics and in vitro and in vivo functional validation studies. This project will identify critical molecular processes involved in breast cancer progression and potential therapeutic targets against breast cancers at high risk for recurrence and poor prognosis. Thus, it is expected that this project will provide future translational research avenues, enhance my position to be at the forefront of cancer research and provide the opportunity to establish myself as an independent researcher following the completion of this fellowship.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF-EF-RI - RI – Reintegration panel

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Call for proposal

(opens in new window) H2020-MSCA-IF-2018

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Coordinator

FUNDACION PUBLICA ANDALUZA PROGRESO Y SALUD M.P.
Net EU contribution
€ 172 932,48
Address
AVENIDA AMERICO VESPUCIO 15 EDIF S2
41092 Sevilla
Spain
Region
Sur Andalucía Sevilla
Activity type
Research Organisations
Links
Total cost
€ 172 932,48