Investigating the role of the tumour microenvironment in lobular breast cancer
This is one of several projects available on a CRUK funded PhD programme at the Cancer Research UK Edinburgh Centre, which is part of the Institute of Genetics and Molecular Medicine (IGMM) at the University of Edinburgh.
Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer after invasive ductal carcinoma (IDC), which account for 10-15% and 80% of breast cancers respectively. ILC is recognized to exhibit a number of clinico-pathologic characteristics distinct from those of IDC. For example, ILC has an unusual pattern of metastatic dissemination having a predilection for spread to the gastro-intestinal tract, peritoneum and ovary. Despite the originally favorable survival, patients with lobular histology have a worse survival in multivariate analysis after a prolonged follow-up which is in part due to extended periods of metastatic dormancy and a lack of response to chemotherapy.
The importance of the tumor microenvironment in tumor behavior is widely accepted and influences both progression and metastatic spread and also therapeutic response. We hypothesize that the interaction of ILC with the tumor microenvironment is critical for the underlying biology that governs their behavior, which is different to IDC. In support of this initial transcriptomic analysis of a series of laser capture microdissected human ILC samples has identified a gene signature that is specific to the tumour microenvironment of ILC. This project will explore the role of both cancer-associated fibroblasts and immune cell populations within the tumour microenvironment in controlling ILC growth, metastatic spread and response to therapy. It will employ a number of molecular and cellular approaches including 3D co-culture models, CRISPR gene editing and mouse models with the aim of identifying new therapeutic opportunities in ILC by targeting the tumour environment.
For further information on how to apply for this project, please visit: https://www.ed.ac.uk/cancer-centre/study-with-us/cancer-research-uk-phd-programme