Cancer Cell Plasticity
Our work focuses on the ability of cancer cells to change their physiological characteristics: cancer cell plasticity. This feature of cancer cells is central to their potential to create and spread tumours around the body, to resist current therapies, and to recur post-treatment. By establishing the mechanisms underlying cancer cell plasticity, we will enable the design of novel therapies that target advanced-stage cancers, and ultimately improve patient survival.
The spread of cancer to distant sites in the body, termed metastasis, accounts for 90% of cancer-related deaths. Despite the high morbidity associated with advanced-stage disease, there are very few, if any, treatment options for patients once a cancer has reached that state. Understanding the biology driving metastatic and therapy-resistant cancer is critical for the design and development of effective therapies to improve patient survival.
Not all cancer cells within a tumour are created equal. In particular, tumours contain subpopulations of cancer cells endowed with a highly aggressive nature, which in turn are linked to metastasis. To date, however, the identity of those aggressive cells, and the mechanisms that determine their aggressive state, remain elusive.
Investigating those questions, our work has disproved the pre-existing hypotheses that creation of aggressive and bulk population cancer cells is a uni-directional process and that residence in the aggressive cancer cell state is a cellular attribute contrived of 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 patients will benefit from therapies that both target the existing aggressive cancer cells and that prevent new ones from arising from their non-aggressive counterparts.
Using in vitro, in vivo and patient tissue models together with the latest sequencing technologies (including RNA-seq, ChIP-seq and single-cell RNA-seq) we are interrogating mechanisms driving 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?
- Do cancer cell plasticity networks underlie the development of therapy resistance?
The Cancer Cell Plasticity laboratory gratefully acknowledges funding from:
The Nelune Foundation’s Rebecca Wilson Fellowship in Breast Cancer Research
The National Health and Medical Research Council
- Diseases We Research
- Breast cancer