Cancer Cell Plasticity Lab

Our work focuses on cancer cell plasticity – the ability of cancer cells to change their physiological characteristics. This feature allows cancer cells to create and spread tumours around the body, to resist therapies and to recur post-treatment. Understanding the mechanisms underlying cancer cell plasticity will facilitate the design of novel therapies that target advanced-stage cancers and ultimately improve patient outcomes.

Background

Metastasis, or the spread of cancer to distant sites in the body, accounts for 90% of cancer-related deaths. Investigating the biology driving metastatic and therapy-resistant cancer is critical for the design and development of effective therapies, to improve survival rates.

Metastasis is linked to highly aggressive subpopulations of cancer cells in tumours. However, the identity of those aggressive cells, and the mechanisms that determine their aggressive state, remain elusive.

Our research has disproved the pre-existing hypotheses that the creation of aggressive cancer cells arises from the cancer cell’s pre-cancer heritage. We have instead demonstrated that aggressive cancer cells are spontaneously, and continually, created throughout the course of tumorigenesis, from the non-aggressive cancer cells comprising the bulk of the tumour. Clinically, these findings suggest that patients will benefit from complementary therapies that both target the existing aggressive cancer cells and prevent new ones arising from their non-aggressive counterparts.

Current work

Using in vitro, in vivo and patient tissue models, together with the latest sequencing technologies (including single-cell sequencing technologies and spatial transcriptomics), we are interrogating mechanisms that drive cancer cell plasticity with single cell resolution, to address the following key questions:

• What are the genetic and epigenetic mechanisms that enable cancer cells to switch from a relatively benign to a highly aggressive cell state?
• What regulatory mechanisms maintain the highly aggressive cancer cell state?
• Which cancer cell plasticity networks underlie the development of therapy resistance?