Biophysical contributions to triple negative breast cancer progression

Background

Triple-negative breast cancer (TNBC) accounts for 15% of the ~34 million breast cancer cases diagnosed annually and is characterised by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC is more aggressive and has significantly higher early relapse rates compared to other breast cancer subtypes. A key factor driving aggressive disease is the high intra-/inter-tumoural and interpatient heterogeneity. TNBC have diverse molecular subtypes, the nature of which remain controversial and are rapidly evolving. Higher extracellular matrix (ECM) stiffness within the TNBC tumour microenvironment has also been associated with poorer prognosis, drug resistance and metastasis. A significant challenge is stratifying patients to ensure treatment regimens are effective: resistance leads to exacerbation of disease during the therapy period and evolution of the tumour microenvironment. There is an urgent need for innovative means to study dynamic changes in TNBC biology.

Aim of the investigation

This project builds on our recent work using innovative multimodal approaches to profile spatial molecular changes in TNBC tissues before, during and after treatment. The overarching goal is to combine advanced imaging of patient-derived organoids with novel bioinformatics and AI-based approaches to define molecular signatures that predict drug resistance and identify new targets for therapeutic intervention.