Novel approaches in overcoming therapy resistance in pancreatic cancer

Suitable for Honours and PhD students

Pancreatic tumours are aggressive and highly resistant to current therapies due to the dense fibrotic stroma, hypoxic tumour microenvironment and immune evasion. Pancreatic tumour cells switch their metabolism to survive better in this hostile environment and recent studies have shown that epigenetic changes play an important role in this adaptation. Studies examining the tumour microenvironment from our lab indicate that aberrant expression of epigenetic enzymes affects therapy-resistance through promoting fibrogenic activation and metabolic switching. Modulating the activity of these epigenetic enzymes in the tumour microenvironment can potentially induce tumour cell death and also enhance the efficacy of other therapies.

HYPOTHESIS

Inhibiting the activity of epigenetic enzymes will reverse the aggressive phenotype of pancreatic cancer cells and enhance chemotherapy and immunotherapy response.

AIM

To determine the role epigenetic enzymes play in therapy resistance in pancreatic cancer.

APPROACH

1. Cellular models and drug treatments.
2. Gene expression analysis by RNA-seq.
3. In vivo mouse model of pancreatic cancer.
4. Spatial transcriptomics and multiplex IHC.
5. DNA and RNA editing using CRISPR-mediated approaches.