A NOVEL drug based on a natural compound found in broccoli, kale and other cruciferous vegetables could hold the key to reversing or even preventing resistance to breast cancer hormone therapy, new research has found.

Scientists from the University of Manchester found that drug SFX-01 ― which has shown promise in a phase II trial (STEM) as a treatment for secondary breast cancer that is already resistant to hormone therapy ― could reverse or even prevent resistance to hormone therapy by blocking a key cancer signalling pathway (a chain of reactions within cancer cells) called STAT3.

It is hoped that SFX-01 could in future be added to hormone therapies such as tamoxifen or aromatase inhibitors from the outset of treatment to increase their effectiveness in patients with primary breast cancer.

In the meantime, while further research is required to confirm the efficacy shown in the phase II trial, scientists hope that the drug could soon provide a new option in treating secondary breast cancer in the clinic.

The study, which also provides a mechanism behind the early success in trials of SFX-01 in secondary breast cancer, is being presented today at the UK Interdisciplinary Breast Cancer Symposium, hosted by Breast Cancer Now.

Breast cancer is the UK’s most common cancer, with around 55,000 women and approximately 370 men being diagnosed throughout the country each year.

Up to 80 per cent of breast cancers are encouraged to grow by the hormone oestrogen and are known as oestrogen receptor (ER) positive breast cancer, which accounts for up to 44,000 cases each year in the UK.

While hormone therapy (which blocks the effect of oestrogen) is very effective in reducing the risk of recurrence for most, around a third of patients with ER positive breast cancer see their disease return within 15 years, and some of these are due to the cancer developing resistance to treatment.

A novel drug SFX-01 ― developed by UK company Evgen Pharma and inspired by a natural plant-derived compound called sulforaphane, which was first discovered in cruciferous vegetables such as rocket, broccoli and kale ― has recently been shown in a clinical trial to delay the progression of incurable secondary breast cancer in women whose disease has already developed resistance to hormone therapy.

In a new study led by Dr Bruno Simões, Dr Sacha Howell and Professor Rob Clarke at the University of Manchester, researchers investigated the effect of SFX-01 alone, or in combination with tamoxifen or fulvestrant, in patient samples and in mice to understand how the drug works and how it can be best used to treat breast cancer.

They found that SFX-01 reduced the ability of specialised cells called breast cancer stem cells to form tumours in mice, with the drug also reducing the ability of breast cancer cells to form secondary tumours in the mice’s lungs.

The researchers then looked at the gene activity levels within the breast cancer stem cells from hormone therapy-resistant tumour samples from patients, finding that the cancer stem cells relied heavily on the STAT3 signalling pathway, which can become active in response to hormone therapy and lead to treatment resistance.

SFX-01 blocked the STAT3 signalling pathway and reversed the effects that may lead to hormone therapy resistance.

In a recent phase II trial (STEM) in patients with ER positive secondary breast cancer that had already started becoming resistant to hormone therapy, 25 per cent of participants benefitted from the addition of SFX-01 to hormone therapy — but the mechanism of why this worked was not known until now.

Further research is now focusing on understanding why certain patients’ tumours are sensitive to SFX-01 and whether an accompanying diagnostic test for activity of the STAT3 signalling pathway could be used to identify the patients that would benefit the most from this treatment.

Dr Simões, Research Fellow at the University of Manchester, said: “Oestrogen receptor positive breast cancer is the most common breast cancer. These cancers frequently develop resistance to hormone therapies, which is a major clinical problem that we are working to address.

“We are excited by our findings that combining standard hormone therapies with SFX-01 could improve treatment of some breast cancer patients by reversing resistance driven by the STAT3 signalling pathway.

“With the success of the recent clinical trial in secondary breast cancer, we hope that further studies will now help to identify which patients may benefit the most from this drug so that it could soon reach the clinic.”

Dr Simon Vincent, director of research at Breast Cancer Now, which helped to fund the study, said:

“It’s really exciting that SFX-01 could in future help to improve the effectiveness of hormone therapies and prevent or treat the return of breast cancer. While hormone therapy is effective for most women, around a third still see their breast cancer return and we urgently need to find new ways to tackle and prevent drug resistance.

“This important discovery reveals exactly how SFX-01 can help overcome hormone therapy resistance and we hope it could now open the door to it being used from the outset of treatment, to prevent resistance from developing in the first place.

“We look forward to results of further trials to fully understand who is likely to benefit most and at what stage of treatment it should be added to hormone therapy to give patients the best chance of survival.

“In the meantime, anyone who is concerned about the risk of their breast cancer coming back can call our free helpline on 0808 800 6000 and speak to one of our expert clinical nurses.”

The study is funded by Evgen Pharma, Breast Cancer Now, The Christie Charitable Fund and the NIHR Manchester Biomedical Research Centre.