Completed Cancer Lungs & Breathing

Imaging the Redox Microenvironment to Predict Tumour Resistance to Therapy

Funder Wellcome Charity-funded
Recipient organisation King's College London
Funding £2.4M
Period Mar 2021 — Feb 2026

In plain English

AI plain-English summary

Lung cancer patients often receive treatments that fail to shrink their tumours, with no reliable way to predict this resistance in advance. The problem is stark: most lung cancer deaths occur because standard treatments stop working in late-stage disease, and doctors currently have no method to identify which patients will be non-responsive. This research aims to develop new PET imaging tracers that can spot the biochemical hallmarks of therapy resistance before treatment begins. The tracers target three specific molecules involved in antioxidant pathways—aldehyde dehydrogenase 1A1, the NRF2 protein, and glutathione synthesis—that cancer cells use to defend themselves against chemotherapy and radiation. If successful, this work would give clinicians a non-invasive tool to identify patients whose tumours are likely to resist first-line treatments. Those patients could then be directed immediately toward second-line therapies or immunotherapy, potentially improving survival rates. The research is currently limited to mouse models of non-small cell lung cancer, but the tracers could eventually be translated to human clinical use. This is fundamental science with a clear translational goal: turning molecular imaging into a practical diagnostic for treatment selection.

View original technical description
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.

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Researchers

Tim Witney (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Imaging drug resistance in cancer to predict response to therapy using a PET radiotracer targeting Nrf2, a key regulator of the tumour antioxidant res
Imaging redox regulation in metastatic cancers
Exploiting the vulnerabilities of drug-resistant lung cancer with theranostics
Molecular imaging of redox processes in cancer
Elucidation of novel molecular mechanisms of radiation resistance and their application to clinical radiotherapy trials

Original classification

Senior Research Fellowship

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.