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Assessing the therapeutic utility of GPX4 inhibition in glioma

16 September 2026 by in PPIE Opportunities

Lay Abstract:

Glioblastoma is the most common and aggressive type of brain cancer in adults. Despite surgery, radiotherapy and chemotherapy, the disease is usually difficult to treat and most patients have a poor prognosis. Treatments that have been successful in other cancers, including targeted therapies and immunotherapy, have had limited benefit in glioblastoma. New treatment approaches are therefore urgently needed.

Our research focuses on a process called ferroptosis, a form of cell death that occurs when cancer cells accumulate damaging levels of oxidised fats. Cancer cells are particularly dependent on systems that protect them from this damage. One important protective protein is GPX4. Blocking GPX4 can therefore cause cancer cells to die through ferroptosis.

We have found that glioma cells lacking the tumour-suppressing protein PTEN are especially vulnerable to GPX4-blocking drugs. PTEN loss is common in glioblastoma. Our results suggest that, when PTEN is lost, cancer cells accumulate particular types of fats that are more easily damaged. Blocking another enzyme, FADS2, which helps produce these fats, also protects the cells from GPX4 inhibition. These findings point to a potential weakness that could be exploited to kill PTEN-deficient glioblastoma cells.

We propose that PTEN loss makes glioblastoma cells more sensitive to GPX4 inhibition by increasing the levels of fats that can become damaged and trigger ferroptosis.

We will test this idea by:

  1. Identifying the fat changes caused by loss of PTEN.
  2. Determining how PI3K signalling contributes to sensitivity to GPX4 inhibitors.
  3. Testing whether drugs that alter fat production can increase or reduce the effects of GPX4 inhibition.

Our ultimate goal is to identify new treatment strategies for patients with glioblastoma.

Role: Need someone who can provide feedback on the project from the patient perspective
Time requirement: One off involvement before submission deadline of 23rd September
Rate of reimbursement: I currently do not have funds myself to reimburse for this.
Criteria for selection: Need someone who can provide feedback on the project from the patient perspective.  
Experiences required: Ideally someone who can comment on the current needs of cancer patients (i.e. unmet needs in cancers where current treatment options are limited).
Deadlines for when you need to hear about interest: No later than evening of 22nd September
If interested, please contact: igor.vivanco@kcl.ac.uk