New drug combination shows promise for breaking BC resistance

cp418

http://www.sciencedaily.com/releases/2015/04/15042...

New drug combination shows promise for breaking breast cancer resistance

(My understanding from various articles is that approx 70% patients are dx as ER+ and approx 50% will eventually develop resistance to either Tamoxifen or AI treatments. This type of research is CRITICAL to prevent recurrence. It should be fast tracked and given high priority for funding clinical trials.)

mike3121

Wow, sounds great. My wife, both ER+ and metaplastic triple negative, has already burned through arimidex, aromasin, and tamoxifen. Now she's to start falsodex after radiation. She just finished her lifetime amount of AC and hopefully it will keep her clear for awhile.

We need this stuff now!

Mike Walsh

JohnSmith

This is promising news. For those who didn't read the article, here's a recap:

Researchers from The University of Manchester working with drug development company Evgen Pharma, have developed a new combination of drugs which could overcome treatment resistance and relapse in breast cancer.

In research to be revealed at the AACR annual conference, the researchers show that in the most common type of breast cancer, affecting 70% of patients, the drug Sulforadex helps overcome resistance to routinely used hormonal treatments by targeting the cancer stem cell population.

While most women initially respond well to hormonal treatment with drugs such as tamoxifen, many go on to develop resistance and relapse. There is evidence that this is often due to activation of the Wnt signalling pathway, a gene involved in development which fuels the growth of the tumour.

Around 70% of breast cancers express the 'estrogen receptor' (ER) and typical treatment focuses on reducing estrogen levels or blocking ER function. However, the researchers have shown that cancer stem cells which cause tumours to regrow and spread do not express the ER. Thus, these stem cells aren't inhibited by the standard treatments and have the ability to regrow the tumour.

The new combination therapy, tested in lab studies by the Manchester scientists, combines Evgen's Wnt pathway-suppressing drug, Sulforadex with standard hormonal treatments. This targets both the estrogen-sensitive cells and the remaining cancer stem cells at the same time.

Dr Robert Clarke from the University's Institute of Cancer Sciences said: "The hormonal therapies we use today are very good at treating breast cancer tumours driven by estrogen.

"However, they don't completely solve the problem. This combination of drugs potentially allows us to target estrogen-sensitive cells, whilst also mopping up the cells which cause treatment resistance."

The study was carried out in lab samples of treatment resistant cells from breast cancer patients. The next step will be to recruit patients for a trial in the next few months.

Dr David Howat, Head of Research and Development at Evgen Pharma said: "We are really excited about the data presented at the AACR. Dr Rob Clarke and his excellent research team have demonstrated the efficacy of Sulforadex in patient derived cancer tissues in vitro and, importantly, in an in vivo setting.

"We now intend to extend this collaboration and advance Sulforadex into a clinical trial with breast cancer patients."

End of article.
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** My thoughts: Sulforadex is a drug based on the natural occurring molecule, Sulforaphane, which is found in cruciferous vegetables such as Broccoli, Brussels sprouts or Cabbages. Sulforadex technology is a patented synthetic and stabilized version of the naturally occurring compound. They were calling Sulforadex as the "Broccoli Pill" last year.
It is a known activator of the Nrf2 pathway, which regulates the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation. Specifically, Sulforaphane is theorized to up-regulate the transcription factor, Nrf2 (which drives the antioxidant response) and down-regulate the transcription factor, NF-kB (which drives an inflammation response). The Nrf2 and NF-kB pathways are commonly cited mechanisms by which sulforaphane exerts its therapeutic effect, although other targets have been implicated and include HDAC inhibition and inhibition of cancer stem cell survival via the Wnt/beta-catenin pathway (either directly and/or indirectly via NF-kB).

Researchers at Montclair State University in New Jersey discussed the benefits of Sulforaphane in this 2013 article: Targeting cancer stem cells with sulforaphane, a dietary component from broccoli and broccoli sprouts, which says: "Combination therapy with sulforaphane and chemotherapy in preclinical settings has shown promising results."

Evgen plans on a Phase I/II breast cancer study later this year. In this pre-surgical "window trial", patients will be dosed with a combination of Sulforadex and Endocrine Therapy for up to 28 days to show safety and tolerance and for biomarker analysis. The trial will be based in England and eventually (maybe) the U.S.

TAGS: SFX-01, SFX01, Sulforaphane, Broccoli pill, Stem-cells.

susan3

my onc told me new resistant drugs were coming out end of this year. Two of them. He told me names, but don't remember. Very cool if they are different ones. Some to come out this year and others to follow . I am resistant, and very much looking forward to these.

Pixiepixie

I read about this too! We all need some good news with regards to new and improved drugs for breast cancer. Let's hope the trial see's positive results

CassieCat

That is very encouraging. Thank you for sharing the link.

Hopeful82014

The sooner the better. I hope this isn't, however, just one more 'near break throughs.'

JohnSmith

It looks like this may take some time to roll out.

I had an email exchange with the Evgen CEO who said
"We are currently raising the capital to do the first trial and that trial will actually be on newly diagnosed patients awaiting surgery (in the UK) - so that we can get proof that the drug is getting to the tumour and moving biomarkers within the tumour.
A trial in metastatic patients will follow in due course, but that is some time off, and still likely to be in the UK.
Best follow our website for progress, regrettably these things take longer to plan, fund and do than many people think."

JohnSmith

Just got an update from the Evgen CEO who says a Phase IIA trial for ER+ metastatic patients will be launched this summer in the UK. This is for their drug, Sulforadex (SFX-01), dubbed the "Broccoli Pill".

The following explains the rationale behind the Phase II clinical trial:
One proposed mechanism for the generation of resistance to endocrine therapy is the proliferation of a hormone-independent clone of breast cancer stem cells (CSCs). Such cells are known to proliferate during treatment with hormonal agents, and can engender a clone of hormone-resistant progenitors which can then repopulate the tumour and render it hormone-independent.
Previously published data has shown that sulforaphane can inhibit breast CSCs. SFX-01 has been shown, by the Group, to inhibit breast CSC activity of both early-stage and metastatic patient-derived xenograft (PDX) tumours and could therefore potentially produce clinically meaningful improvements to endocrine therapy. The Directors believe that SFX-01 has the potential to be a well-tolerated treatment which may prevent the onset of resistance in early breast cancer, thus increasing chances of cure, and significantly delaying the onset of hormone resistance in both pre and post-menopausal women in the advanced metastatic setting.
The objective of SFX-01 therapy is to reduce the number of CSCs proliferating in those tumours which are treated with anti-hormonal agents, and prolong the duration of response. The proposed clinical study is a randomised study in patients with ER+ metastatic breast cancer who have failed on prior adjuvant, or first-line aromatase inhibitor therapy. The proposed study is risk-managed, with a Phase IIa component comprising 40 patients. This will allow for an early efficacy signal based on tumour volume, to determine if there is preliminary evidence of efficacy.
Provided that there is evidence of activity, the intention (subject to further funding) is to advance SFX-01 into a Phase IIb trial in 160 patients, with progression-free survival as the primary clinical endpoint.

TAGS: SFX-01, SFX01, Sulforaphane, Broccoli pill, Stem-cells.

MusicLover

JS, Thank you for the update.

Fallleaves

Thanks for the great information cp418 and JohnSmith! This sounds very promising. Glad to see they are moving forward with a clinical trial. In the meantime I'm gonna switch over to sulforaphane after I finish up my DIM.

Kathy044

For those interested Karen Collins, in her Smart Bytes blog, interviews an expert on how to make the most of the sulforaphane in broccoli and other cruciferous vegetables. It's complicated but it is better to prepare the veggies by blanching first.

http://www.karencollinsnutrition.com/smartbytes/2013/11/21/broccoli-in-a-diet-to-reduce-cancer-risk-raw-or-cooked/#more-1466

Thanks cp418 and John Smith for this research news and for reminding me why it is important to steam kale or to add a little bit of kimchi to my plate when eating in a salad raw.

Kathy

Heidihill

Broccoli sprouts are supposed to have the highest concentration of sulforaphane. I had them everyday for a whole summer once, ordering them through a health food store. On my next scan I had developed a thyroid nodule. At least I was still NED! The thyroid nodule has since shrunk on scans, maybe because I cut down on goitrogenic foods or started cooking them more to lessen the effect on my thyroid. I would do it again though because it might have killed some cancer stem cells early on.

DivineMrsM

It's great to learn about this new drug combination and its potential to extend lives. Hope all those clinical trials lead to one more effective treatment in regards to bc

JohnSmith

Good news. A Phase II clinical trial has been approved to explore the efficacy of Sulforadex (SFX-01) in metastatic ER+ patients.

To recap what I wrote last year,
Sulforadex (SFX-01), aka the "Broccoli Pill", is a drug synthesized from the chemical compound "sulforaphane" found in cruciferous vegetables such as broccoli, brussels sprouts or cabbages.
Some researchers theorize that a key mechanism of resistance to current hormone therapies is the proliferation of hormone-independent breast cancer stem cells. Pre-clinical data of Sulforadex (SFX-01) revealed inhibition of breast cancer stem cells.
This trial will start in Manchester, UK (Christie NHS Foundation Trust) and open up to other sites across Europe, enrolling ~60 patients with ER+ metastatic breast cancer. Patients will be enrolled into one of three study arms (SFX-01 in combination with either aromatase inhibitors, tamoxifen or fulvestrant).

Aug 2016 Press Release: http://otp.investis.com/clients/uk/evgen_pharma/rns/regulatory-story.aspx?cid=1240&newsid=77452 (Link appears bad)
Aug 2016 Media link: http://www.liverpoolecho.co.uk/news/business/liverpool-drug-firm-start-human-11765790

TAGS: SFX-01, SFX01, Sulforadex, Sulforaphane, Broccoli pill, Stem-cells, Nrf2, NF-kB, Wnt

cp418

Thank you for this update!