Research at Blood Cancer UK – How existing drugs could potentially be used to fight blood cancer

At the Blood Cancer UK (at that time the charity was known as Bloodwise) Impact Day in September 2018 Dr Farhat Khanim was one of the research scientists who’d agreed to share their current work with the attendees.   She’s a Blood Cancer UK funded scientist who is wonderfully passionate about her work and fully believes in the research they are doing #reassuring

Dr Farhat Khanim Bloodwise Impact Day
Dr Khanim giving her speech at the Bloodwise – Blood Cancer UK Impact Day in 2018

This blog covers what Dr Khanim shared about the research they are currently working on.

I Hope, like me, it gives you the sense that the answer is just around the corner and that at Blood Cancer UK they are definitely on the right path.  For me and my family to hear this, as I was diagnosed with Acute Myeloid Leukaemia in 2015, was a great comfort and because we do a lot of fundraising too (this has turned out to be quite a long post but it’s well worth reading because you will feel a lot more positive about the future believe me).

Dr Khanim’s focus;

Dr Farhat Khanim is based at the School of Biosciences in the University of Birmingham and is a molecular/cellular biologist working in the field of Haemato-oncology. Amongst other things she is a member of the Translational Haemato-oncology research drug re-purposing group with the main purpose of the identification and delivery of effective, non-toxic therapies for blood cancers to the clinic.

To achieve this goal the group studies the basic biology of haematological malignancies, performs drug redeployment screening and drug mechanism of action studies. Mechanistic studies include analysis of tumour metabolism in response to drugs and tumour niche interactions.

farhat_khanim bloodwise cancer research leukaemia
Dr Farhat Khanim (Right) with research team

Dr Khanim’s speech;

“Firstly a little background about me; for six years I worked in cancer research which satisfied the intellectual part of me but I wanted my work to make a difference, to know that I was going to actually help patients.   In 2003 I met Professor Chris Bunce and Professor Mark Drayson and joined the Bloodwise (Blood Cancer UK) family on a postdoc programme grant.”

“So what we do is try to understand how cancers develop, what goes wrong, what happens normally in our bodies and then what goes wrong to give rise to the tumours.  Understanding this then leads into the development of treatments.”

The Drug Development Process – how drugs get into the clinic?

“Traditionally this starts with a target, a certain pathway (tumour), that’s been identified through academia which is then screened for compounds that may target that particular pathway.  After this there is a huge series of steps which takes a long, long time to go through in order to develop a drug.  This ‘model’ that we use is based on the same one used in the pharmaceutical industry too.  Our target being a mutation or a pathway of a tumour cell.

When the pharmaceutical industry is developing a new drug it usually takes between 12 to 15 years and costs an average of two billion US$.  Although this does work it’s not really cost effective for us and by using this model we are not going to get new treatments rapidly into the clinic which is what we want to do.  In reality this model works well for drugs to treat conditions the affect lots of people but when you have rarer conditions (many blood cancers are classified as rare diseases because they don’t effect huge numbers of people) then they are not a priority for the pharmaceutical industry so we have to ask ourselves how do we find treatments for these people.  Also the moral questions is how do we find treatments for people who don’t live in developed countries where there isn’t the investment in diseases that affect them? 

One of the research projects we worked on a while ago;”

A Promising Drug combination (findings published in 2015) BaP;

Bezafibrate (lipid lowering drug used for cholesterol) with Medroxyprogesterone (used in contraceptives and HRT)  =  BaP.  

In the lab its been shown that this combination kills tumour cells and doesn’t damage healthy cells.  It is also good at killing tumour cells in Burkitt Lymphoma which does affect a lot of people in the west but predominantly children in Africa, it accounts for half of the cancers in children there.  Scientists did a huge amount of science to understand how these drugs work and found that these drugs target multiple pathways so they do multiple things to the tumour cells.  So they took BaP into trial which was a big step.  20 AML patients were treated; these were end stage patients, they had nothing else left to try, they’d had every other treatment possible.  Of these 20 patients researchers saw haematological improvements in 11 of them, one lived an extra three and a half years.  Next they did a dose escalation study (increasing the amount of these drugs given to the patient) but found very rapidly that it became toxic ie their kidney function became bad.  They also did a trial in Africa with 98 children with Burkitt Lymphoma and saw haematological improvements in all of them and importantly saw no toxicity.

“All of this took a long time so we started to think of if there was a way of speeding this process up.  This is where CARDe – Centre for Accelerated Drug Re-deployment comes in; Click here for full description of the CARDe

Drug Re-deployment or Re-purposing;  This is the use of existing drugs for a new indication.  The drug development pipeline has generated a significant impact in the form of new therapies, especially in areas of unmet needs.

How the Drug Re-deployment Pipeline is being developed at Blood Cancer UK

“To start this we took a random selection of 100 drugs from the British National Formulary also known as the BNF which lists all of the UK’s medicines available for use in the clinic and is used by Doctors, Pharmacists, Nurses and so on.  We added some chemotherapy drugs for controls and tested all of them on the tumour cells of Leukaemia, Lymphoma and Myeloma. 

There are actually thousands of drugs in our pharmacies with 1200 routinely used so what potential do those drugs have? What we have done so far has barely scratched the surface, the academic community and its pharmaceutical partners are very excited about this drug re-purposing development because;

  1. these drugs are available
  2. familiar in the clinical setting
  3. associated with limited toxicities
  4. importantly these drugs are cheap

One of the things that’s so good about these drugs (many of which are available to buy over the counter in our Pharmacies) is that we already know they are safe and they are already used by clinicians which means that we may or may not need to do the animal studies and we can take a lot of the usual processes out of the equation.  Therefore we can potentially move quickly onto the phases where we check the safety and efficacy, the reviews, approvals and then hopefully we can get a new drug into clinic as a new treatment.

What we found was that while some of them had no effect whatsoever some were identified at being quite potent at killing tumour cells in the lab.  We studied these drugs to try to understand how they were working and as a scientist this scratches the intellectual itch because we learn new things and at the same time about cancer. 

We then started to look at combinations of some of these drugs together because we want to batter these tumour cells hard, so that there is no way the cell is going to get around what we are doing to it.

BaP looked promising but the fact that we couldn’t escalate the dose meant that we needed to add in a third drug so we went back to our ‘library’ (which is called the FMC after Farhat, Mark and Chris as we couldn’t think of anything better to call it!).  One we are looking at is Valporate (used to treat Epilepsy) with BaP so VBaP.  We are in the process of designing a national clinical trial for MDS (Myelodysplasic Syndromes) and will be applying for funding shortly.  This will be the first trial in MDS aimed at Haematological improvement rather than just patient management.

Another one we have been researching Zinc and Colchicine (used to treat Gout) ZaC to treat Burkitt Lymphoma.  This combination has proven very effective but what is also very exciting is that we have found that there may be potential for Zinc to be used as a prevention drug as well. However we need to do a lot more science before we can demonstrate that but still it is very exciting.

We have also been looking at the combination of Valporate and Niclosamide (tapeworm treatment), VaN for treatment of Myeloma.  Niclosamide has proven to have a high amount of anti tumour activity.   We’ve looked at producing derivatives of Niclosemide which will go directly to the bone marrow of Myeloma patients in order to get a higher dose to it.  We’re writing up the data at the moment so we can take this into clinical trial.

While we’ve been doing all of this we have also been learning lots of new things about disease biology that we didn’t know before.  Such as what goes wrong in a tumour cell and how we may be able to take advantage of that and kill these tumour cells.”

“All of these drugs are safe to give to people and are oral which means we can potentially move them to clinical trial very quickly which is very important.  Also another point about all these drugs is that because they are all oral drugs, potentially patients can have treatment at home, ” Dr Farhat Khanim

Dr Khanim on Blood Cancer UK;

“Blood Cancer UK is one of the few agencies that supports research long term;  If you want to see the benefits of research long term you need to invest long term, in individuals and concepts, this is very important.

What is also so good about the Blood Cancer UK ethos is that they share all of their findings and because of this some of our results are now also being used by ovarian, bladder and head and neck cancer researchers.

Having worked worked in this community for 15 years the point I would like to make is that Blood Cancer UK is making a difference, it genuinely is happening.  Your fundraising is making a massive difference, it’s what makes everything possible.  So as a researcher who set out many, many years ago to try to make a difference, without you and all of the work that you do I wouldn’t be able to achieve my goal and more importantly I wouldn’t be able to achieve our goal so thank you from me…”

I am one of the people who spends all of the money you raise, Dr Farhat Khanim

Dr Farhat Khanim Bloodwise blood cancer research
Dr Khanim in her lab at Birmingham University

Blood Cancer UK has three expert committees which consider and review grant applications after they’ve been reviewed by experts around the world.  Their expertise means that the charity only funds the very best research and don’t do research for research sake.  They only fund research that will benefit patients and are currently responsible for over 400 leading researchers in over 160 projects across the UK.

I hope you have found this as interesting as I did and remember this is just a part of the research being funded by Blood Cancer UK.  And don’t forget they share all of their findings with all cancer researchers. Thanks for reading my post >> ButterflyinRemission

butterfly in remission anna mamwell leukaemia blog

Click here for more on the research funded by Blood Cancer UK >> Three Birmingham research projects to beat blood cancer

Bloodwise blood cancer awareness month leukaemia aml
Facing blood cancer together – the Bloodwise Forum

If you have been affected by blood cancer and would like support or have something you’d like to ask another person in the same position please go to >> Blood Cancer UK Support Forum

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