Radiotracer lights up treatment-resistant NSCLC
A radiotracer could identify treatment-resistant NSCLC cancers on PET scans and predict resistance before treatment initiation.
Researchers from King’s College London (UK) have demonstrated that a radiotracer can light up aggressive cancers on PET scans, informing clinicians of treatment resistance or failure before treatment starts. This could allow for alternative therapies to be quickly administered and prevent patients from receiving prior unnecessary treatment.
Therapy resistance remains a massive problem in oncology and has resulted in little improvement in NSCLC survival rates over the last 10 years, despite advancements in prevention, screening and treatment options. It has previously been found that NRF2 activation is linked to resistance.
There is a lack of non-invasive methods for identifying NRF2-linked resistance in NSCLC patients who are in the early stages of treatment and patients typically must undergo 12 weeks of treatment before receiving a PET or CT scan to determine efficacy. If treatment resistance is identified at that point, it may be too late to change their course of treatment, often leaving end-of-life care as the only option.
“We wanted to increase the window of opportunity for treatment for these patients – giving them more choice and a better chance of survival” commented Tim Witney, lead author of the study.
To address this, Whitney and the team used an existing PET radiotracer termed 18F-FSPG, which binds to the tumor-associated protein xCT and can highlight NFR2 activation in both orthotopic, patient-derived and mouse models of NSCLC. This approach lights up tumor-resistance cells brighter than treatment-responsive tumors, allowing clinicians to identify treatment resistance before a patient has begun treatment.
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The researchers also demonstrated that an antibody-drug conjugate can target xCT and selectively kill these cells. Further research is required into this but it highlights a potential treatment option for the most aggressive cancers.
“With this technique, we can give the right treatment to the right patient, making it more cost-efficient for the NHS and providing hope for patients with aggressive tumors,” commented Whitney.
This study has laid the groundwork for future research into the use of radiotracers to identify aggressive cancers, allowing for better targets and treatment. The researchers are continuing their work by conducting a Phase I clinical trial (NCT05889312) of 35 NSCLC patients, where they will use a whole-body PET scanner to identify xCT before and after treatment.