'Broccoli-based' drug could help treat breast cancer

A new drug based on a compound found in cruciferous vegetables could improve the effectiveness of breast cancer hormone therapies, new research suggests.

Scientists at the University of Manchester found that the drug SFX-01 could reverse or potentially prevent resistance to hormone therapies by blocking a chain of reactions within cancer cells known as STAT3.  

Up to 80% of breast cancer cases are known as oestrogen receptor (ER) positive breast cancer, since the disease’s growth is encouraged by the oestrogen hormone.

Hormone therapy can be very effective in reducing the risk of recurrence, though it’s thought around a third of patients with ER positive breast cancer see their disease return within 15 years, with some cases being attributable to patients developing resistance to treatment.

The team in Manchester assessed how SFX-01 worked by itself, as well as in combination with the hormone therapies tamoxifen and fulvestrant. The drug was tested both in patient samples and mice to see how it can be used to treat breast cancer. They found that SFX-01 reduced the ability of breast cancer stem cells to form tumours in mice, while also reducing the ability of breast cancer cells to form secondary tumours in the mice’s lungs.

The researchers also examined gene activity levels within the breast cancer stem cells from hormone therapy-resistant tumour samples from patients, discovering how cancer stem cells relied heavily on the STAT3 signalling pathway. STAT3 is able to become active when hormone therapy is used and ultimately lead to treatment resistance. However, the researchers discovered that SFX-01 was able to block the STAT3 signalling pathway and reverse the effects that may lead to hormone therapy resistance.

The drug - developed by UK company Evgen Pharma - has previously shown promise in a phase II trial as a treatment for secondary breast cancer that is already resistant to hormone therapy. That trial showed that SFX-01 was able to delay the progression of incurable secondary breast cancer in women who had already developed resistance to hormone therapy.

The drug was inspired by the natural compound sulforaphane, which is abundant in vegetables such as rocket, broccoli and kale.

The scientists in Manchester now hope that the drug could be added tamoxifen or aromatase inhibitors to increase those drugs’ effectiveness in patients with primary breast cancer. More so, the team hopes that SFX-01 could be used as a new option to treat secondary breast cancer.

The study results were presented at the UK Interdisciplinary Breast Cancer Symposium, hosted by the charity, Breast Cancer Now, in Birmingham. 

Co-author of the study Dr Bruno 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.”