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“Olive Oil” Drug May Benefit Some Brain Cancer Patients, Study Suggests

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A unique drug derived from oleic acid – which naturally occurs in animal and vegetable fats such as olive oil – has shown promise for patients with an advanced form of the most common type of brain cancer, following a study led by The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London.

Results from the multi-centre Phase 1/2 study, which have been published in the British Journal of Cancer, suggest the drug could be particularly effective for patients with glioblastoma, an aggressive type of brain cancer which affects 3200 people across the UK each year.

One patient experienced an exceptional response

Following these results, the drug is now being trialled in a global randomised Phase 2b/3 study focused on newly diagnosed glioblastoma patients, which is recruiting patients at The Royal Marsden.

The drug, named 2-OHOA, is a first-in-class treatment – which means it offers a new and unique way of treating the disease - and is designed to block the growth of cancer cells.  

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The early study enrolled 54 patients with recurrent glioblastoma and other advanced solid tumours. Of the 21 patients with glioblastoma treated, around a quarter (24%) responded to the drug and one patient experienced an exceptional response, which lasted for more than three years.

Drug alters cancer cell walls

2-OHOA is a synthetic lipid derived from oleic acid that works by restructuring the abnormal membranes of cancer cells. Lipids are a broad group of organic compounds which include fats and waxes, and they play an important role in the structure of cell membranes. Cell membranes are the exterior layer of a living cell and help to regulate its growth.

The abnormal membranes of cancer cells make it easier for proteins within each cell to meet neighbouring proteins. This creates signals, which drives the disease’s growth. 2-OHOA blocks these signals by making the membranes of cancerous cells act like normal cells, putting the brakes on the abnormal growth signals driving cancer progression.

Including brain cancer patients in early phase trials

Phase 1/2 study lead Dr Juanita Lopez, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Reader in Early Phase Drug Development at The Institute of Cancer Research, London, said:

“Glioblastoma is an incredibly difficult disease to treat and patients with advanced disease have very poor outcomes, often living for just a year after their diagnosis. There hasn’t been an effective new treatment for this patient group in nearly two decades, so drug development urgently needs to be accelerated. 

“Unfortunately, patients with brain cancer often don’t have the opportunity to participate in early phase trials. This underpins the vital importance of research into novel new drugs like 2-OHOA, which is designed from the same building blocks as olive oil. The drug works by reshaping the walls of cancer cells, blocking crucial growth signals that drive cancer. By including glioblastoma patients on this study, we were able to more quickly show early and hopeful results, supporting their inclusion in the Phase 2b/3 trial. We’re very much looking forward to results from ongoing trials and hope this treatment eventually becomes widely available.”

The trial has 'given me hope'

After being diagnosed with glioblastoma in March 2023, Michele Treen, 42 from Crawley, quickly reorganised her wedding and got married a week before undergoing brain surgery. She was then referred to The Royal Marsden where, along with being treated with radiotherapy and chemotherapy, she joined the phase 2b/3 trial for 2-OHOA. She recently had her fourth stable scan in a row. Michele said:

“I was meant to be getting married in July 2023, but when we found out about the brain tumour, we wanted to do it straight away. Thanks to our incredible friends and family, me and my husband, Aaron, somehow pulled off a wedding in two weeks. We were so happy and so sad that day, crying all the way through. After the wedding, the first thing we did as a married couple was attend another appointment where we were told that the tumour was grade four and incurable. Our entire world came crashing down.

“I recovered well from surgery and, when I was told about the trial, I thought, why not? There’s nothing to lose. The drug comes in a sachet – a bit like Lemsip – and I take it with water three times a day. I experience some side effects, like fatigue and nausea, but we don’t know if that’s from the drug – which could be a placebo – or my ongoing chemotherapy. Either way, I feel fine and can still do things I love. For example, I spent the summer traveling across Europe with my husband and 11-year-old daughter in a motorhome. From mountain-biking in Andorra to exploring Venice’s canals, I did things I’ll never forget with the people I love most.

“The Royal Marsden is the most incredible hospital I’ve ever been to and everyone, from the reception staff to the nurses and doctors, are all so kind. It was amazing the hospital offered me the chance to join this trial, which has given me hope.”

Reference: Lopez J, Lai-Kwon J, Molife R, et al. A Phase 1/2A trial of idroxioleic acid: first-in-class sphingolipid regulator and glioma cell autophagy inducer with antitumor activity in refractory glioma. Br J Cancer. 2023;129(5):811-818. doi: 10.1038/s41416-023-02356-1

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