Imaging the Redox Microenvironment to Predict Tumour Resistance to Therapy

The majority of lung cancer deaths result from ineffective treatment of late-stage disease. Currently, there is no satisfactory way to identify patients that will not respond to standard-of-care treatments.

Positron emission tomography (PET) imaging offers a potential solution to this clinical problem through the non-invasive assessment of molecular processes that underpin therapy-resistance.

The identification of cancer patients that are refractory to treatment will allow the selection of second-line therapies that have the potential to improve patient response and survival.

For this SRF, I will develop novel PET radiotracers to predict therapy resistance in mouse models of non-small cell lung cancer.

These radiotracers will non-invasively image the aberrant activity of key antioxidant pathways that are causal to therapy resistance.

Specifically, I will use structure-activity relationships and in vivo imaging to design highly-specific radiotracers for the cancer stem cell marker, aldehyde dehydrogenase 1A1; nuclear factor erythroid 2-related factor 2, the master regulator of the antioxidant response; and de novo glutathione synthesis.

Our library of redox radiotracers will subsequently be used to detect drug resistance in syngeneic, isogenic and patient-derived models of lung cancer.

Finally, I will use the radiotracers developed in this programme to assess response to immunotherapy in drug-resistant lung cancer.