Our research
Problem
The standard-of-care treatment for advanced, metastatic cancer is chemotherapy. However, this relief is short-lived as resistance to chemotherapy inevitably develops in the majority of patients. Chemoresistance remains a major barrier in treatment efficacy and patient survival. Underpinning this are the multitude of interactions happening within the tumour microenvironment between cancer cells and surrounding stromal components, all of which protect the tumour from drug-induced adversities.
Understanding these interactions is key to improving the outcomes for cancer patients.
Solution
Although the molecular landscape of cancer is complex, the critical role of the tumour microenvironment in cancer growth and survival suggests it is vulnerable to intervention. As such, we aim to improve the survival rate of advanced cancer patients by deciphering and therapeutically exploiting elements of the tumour microenvironment that facilitate chemoresistance.
We achieve this by first, characterizing the interactions in the tumour microenvironments. This includes investigating the role of cancer associated fibroblasts (CAFs), immune cells, extracellular vesicles (EVs) and the extracellular matrix in facilitating tumour progression.
Using these insights, we then aim to ‘re-shape’ the tumour microenvironment by modulating these pathways, effectively re-sensitising the tumour to chemotherapy and improving treatment efficacy.
Impact
Our group utilises novel technologies to investigate components of the tumour microenvironment that promote tumour progression and impair treatment efficacy. These include:
- 3D in vitro models of cancer using spheroid co-cultures and patient-derived organoids to investigate key pro-tumour signaling pathways and assess drug response, better replicating cancer biology than 2D cultures,
- Imaging mass cytometry to enable multiplex in situ imaging of tissues at the single cell level, a high throughput method of assessing the metabolic signatures of cancer and stromal cells,
- Liquid chromatography coupled with mass spectrometry (LC-MS) to characterize metabolites secreted by stromal cells
By harnessing these cutting-edge technologies, we have begun to better understand the complexities of cancer metabolism, immunosuppression, and molecular communication pathways. This serves as a foundation for our ongoing projects, where we are continuing to probe for vulnerabilities within the tumour microenvironment to inform novel treatment strategies.
Current projects
Exploring the role of metastasis suppressor NDRG1 in the packaging and activity of small extracellular vesicles secreted by pancreatic cancer cells.
Exploring the roles of Vitamins D and E on signalling pathways between breast cancer cells and the tumour microenvironment.
Investigating novel targetable mechanisms of metabolic cross-talk between pancreatic cancer cells and fibroblasts to improve response to current chemotherapy.
Examining how metabolic cross-talk between cancer cells and fibroblasts influences the immune micro-environment.