Chee J, Stevens K, Principe N, Chin M, Vittorio, O, Phung AL, Gray N, Trivedi, P
Funding: WA DOH Future Health and Research Innovation Fund, Raine Foundation, NSW Dust Diseases Board, Cancer Council Western Australia
Lay Synopsis: Tumours can reshape how immune cells use energy and nutrients, making the immune system less able to attack cancer and reducing the effectiveness of immunotherapy and chemotherapy. We will test whether existing metabolic drugs can be repurposed and combined with standard treatments to create new, more effective therapeutic strategies, and use gene editing, metabolomics, and spatial imaging to pinpoint the pathways to target and guide development of next-generation metabolic–immunotherapy combinations.
Scientific Synopsis: Cancer can “rewire” how immune cells use energy and nutrients, making them less able to attack tumours and reducing the chances that treatments work. We are investigating how metals and fats inside tumours influence immune function, and whether safe, existing metabolic drugs can be repurposed to boost responses to immunotherapy and chemotherapy. Our goal is to help match patients to the treatments most likely to work. This will be achieved in the following aims:
- Boost treatment response with repurposed metabolic drugs:
Test whether targeting tumour immune metabolism improves immunotherapy and chemotherapy responses in preclinical cancer models. - Prove the key pathways that drive resistance: Use CRISPR gene editing in tumour and immune cells to identify which metal- and lipid-handling pathways causally control anti-tumour immunity and therapy response.
- Reveal what changes inside tumours during treatment: Measure metabolites and metal levels in blood, and map the spatial distribution of metabolites and metals within tumours (metabolomics, MALDI imaging mass spectrometry, and high-resolution metal imaging). Integrate these profiles with patient outcomes such as therapy response and statin use.