Internet friends: help me answer a question!

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I’m currently working on a new video for Cancer Research Demystified, where I’m going to attempt to answer this lofty question. What is the biggest challenge in cancer research today?

For the video, I’ll summarise a few different perspectives on this: the patients, the advocates, the funders, the institutions, the public, and the researchers ourselves. The most common answer so far is of course ‘there’s more than one!’ so I’ll cover as many as I can, and give my two cents on what could be considered the one single greatest challenge.

The NCRI cover their top priorities here – (of which there are of course more than one!) and you can see similar lists from many other groups. But what is the biggest one?! I’ve been asking around on Twitter, Instagram and Facebook, and I’ve gotten 24 responses so far, mostly from other cancer researchers, but some from patients & funders too. Before I compile, compare & contrast these, I wanted to ask you too – what do you think is the single greatest challenge in cancer research today? I’ll give you a head start by saying that the answers I’m getting are falling into two few common themes: biology & barriers.

Does one of these jump out at you as being a bigger challenge than the others? Do you have something to add? Comment below or DM me on Twitter/Facebook/Instagram/Reddit/LinkedIn and I’ll discuss your thoughts (anonymised if via DM) in our upcoming video!

Human tissue models for the replacement of mice in cancer research: Are we there yet?

I recently came across a review which asked if it’s time for peer reviewers to request ‘organ on a chip’ models instead of animal validation studies, and it got me thinking – are we there yet?

https://pubmed.ncbi.nlm.nih.gov/33240763/

As cancer researchers, if we submit an article for publication that contains only data from cell lines, we’re often asked by peer reviewers to carry out animal studies – usually in mice. This review suggests that it might be nearly time for reviewers to ask for human tissue work instead – maybe some of our newest human tissue models are good enough to replace these types of animal studies?

Personally, I’m a big advocate for human tissue work in cancer research. Anyone who collaborates with me knows that I favour ex vivo / 3D culture of human tumours over mouse models. Of course there are ethical considerations here around reducing the number of animals used for research, but my opinion stems mostly from the science – because of the very simple fact that mice are not humans. The differences between mouse biology and human biology are too wide ranging, with far too many variables to feasibly take into account. Frankly, neither have been characterized rigorously enough to pick apart their similarities and normalize for their differences.

Of course, to date, mouse xenografts (and more recently, patient derived xenografts) are pretty much the best models we’ve got in terms of testing new cancer drugs in a better model than cell lines, without the ethical risks of testing them in living humans too early.

As such, many scientists like me around the world have been developing a huge range of human tissue models, usually removed from a cancer patient at biopsy or surgery, and donated for research. The idea being that one day we’ll get these cells or tissues to survive outside the body while changing as little of their biology as possible, and treat them with experimental drugs for research. Ultimately, replacing animal models.

Roughly speaking, these types of models fall into three categories: explant cultures, organoids/tumouroids, and ‘organ on a chip’ models.

Explant cultures involve taking a small piece of donated human tissue, and trying to keep it alive for a few days in an incubator, helped along by different nutrients and materials. One of the main benefits of explants is that the tissue stays whole, rather than the scientist isolating out particular cell types. The original architecture of the tissue, and range of different cell types within it can remain somewhat intact (this isn’t perfect, but it’s improving). I’ve been using a version of explants for the last five years, testing new drugs in prostate cancer, as part of my fellowship project ‘SCREEN’, kindly funded by Prostate Cancer UK.

Organoids, or specifically within our field of cancer research – ‘tumouroids’, represent human tumour cells that are grown in 3D outside of the human body, including multiple key cell types and environmental factors. Here the structure of the tissue does not remain intact as with explants, but key molecular signals added by scientists can induce the cells to organise themselves in the same way that the original tumour would have done in the human. These can be cultured for longer than explants generally, and offer more flexibility for the researcher to tweak particular aspects of their behaviour.

Organ on a chip models can be based on either of the above, but include additional extras like midrofluidics (a system that allows for nutrients to flow over and around the cells in the same way blood would in the body), which can encourage blood vessels to grow and feed the tumour, as they would in a human. These are getting ever closer replicating human tumours outside of humans.

But are any of these good enough to replace mouse experiments yet? My gut says no – but we really are very very close.

One of the issues with this branch of cancer research is that there are just so many different types of models being investigated. Yes, they do fall roughly within three categories, but within each of these categories, there are dozens if not hundreds of iterations being researched around the world. In my view, to properly validate them, we need a consensus – not a new model every five minutes! This consensus will be difficult to achieve, as within the structure of academic research we are encouraged to generate new intellectual property (IP), and we’re generally taught that to get a model validated and used in the clinic, we need to either commercialize it ourselves, or licence it to a company who will develop it for us. This is the approach that will get us the next grant, the next paper, the next promotion – i.e. more cred, and potentially personal financial gain. So why would we bother to further develop, independently validate and rigorously characterize someone else’s model, when we could be changing it slightly to add our own ‘unique selling point’ and branding it as our own?

My hope is to reject this way of thinking. Over the first few years of my new lab, I am to compare and contrast the leading models from around the world in a fully independent setting, where I’m not backing any horse in the race – where I have no allegiance to one human tissue model over another – and just purely try to see if the best one(s) reflect how humans actually respond to anti-cancer treatments. If we can pull this unbiased validation and rigorous characterization off, then I truly believe the peer reviewer mentioned in the paper linked above should absolutely be asking researchers to validate their research in these human models rather than animal models.

It’s worth mentioning that I also tweeted this paper and got varying responses. While one person replied a jokey ‘I wonder what reviewer 3 wrote in the report :)’, another expressed caution:

And I agree somewhat – we still don’t have strong enough validation in my mind to fully replace animal studies. But should reviewers be requesting more human work incrementally as our models get better and better? Yes, I think so. They’re certainly worth carrying out in addition to animal studies – just maybe not instead of animal studies just yet.

Dr Dania Movia from Trinity College Dublin commented on the frustration of human tissue researchers still being required to validate their findings in animals instead of humans – why do we think of mice as a gold standard for how human biology behaves? It makes no sense, and I couldn’t agree more! While mouse models bring some valuable extra data that human models don’t have perfect yet, they’re certainly imperfect in a lot of other ways, and not the right place to validate a human model.

Check out the review linked at the top of this blog if you’d like to read a more technical summary of where the field is at (though the review is not specific to cancer research). And let me know what you think! Are we ready to replace animal models with human models today? Will be there in a year, in a decade, or ever?

A tour of our lab!

A quick blog this week! I wanted to take a moment to introduce one of our favourite Cancer Research Demystified videos. Here, we give a tour of our lab so that cancer patients, carers, students and anyone with an interest can see what cancer research really looks like!

During our first couple of years meeting with cancer patients, myself and Hayley noticed that for a lot of them, their main frame of reference for what a science lab looked like was ‘the telly’. Whether it was CSI, or even a particularly slick BBC News segment, it was clear that research labs were expected to be minimalist, futuristic, and full of coloured liquids.

The occasional person would describe the opposite picture – dark wooden cabinets filled with dusty glass specimen jars, stained benches, blackboards, worn-off labels on mystery chemicals, and that strong, ambiguous, smell.

Of course, neither are accurate. Real cancer research labs are somewhat modern, sure, but even the most expensive and ‘futuristic’ equipment typically looks more like a tumble dryer than an interactive hologram, and though much of our equipment does use lasers – they are hidden deep inside rather than scanning the lab for spies! Blackboards are long gone, replaced with white boards, dusty unlabeled jars are disposed of due to strict health and safety protocols, although stains on benches….? Well, some of those remain.

We did initially face some mild resistance when we first attempted to film this video. A senior member of staff advised us that patients want the comfort of knowing that the best brains in the world are working on a cure, using the best technology and most impressive workspaces. That’s why, we were told, we need to clear out so much lab mess before the camera crews come in for a news segment.

But frankly – those perfect, sterile, swish labs are out there – if someone wants to see a scientist in a never-before-worn white coat pipetting some pink liquid into a plate, all they need to do is turn on the news. We wanted to show something different – and frankly, more honest – warts and all!

The video we ended up with is a little on the nose perhaps, but we felt it needed to be. We show the reality of what it’s like to work in a lab (well, close to reality anyway – we filmed after hours to avoid getting in people’s way, so it is unusually quiet). Some of the difference between day-to-day lab work versus office work are highlighted, such as not being able to eat, drink or touch up your make up within the lab, and having to wear appropriate PPE.

I came back to this video during lockdown because I missed the lab. I still haven’t been back in there, and I’m not sure when I next will be. Other people are back there now though, under strict covid protocols, with significantly reduced capacity and masks. I hope to join them one day, but for now I’m minding my asthmatic lungs at home!

If you’re a cancer patient or carer – here’s a real look at where we’re carrying out the research to build better diagnostics and therapeutics. If you’re a student thinking about doing a medical/biology based research project – this is the sort of place you’ll find yourself working. Please enjoy!

For more Cancer Research Demystified content, here’s where you can find us:

YouTube: https://www.youtube.com/c/CancerResearchDemystified

Twitter: @CRDemystified

Instagram: cancer.research.demystified

These blogs come out every Monday at 11am GMT – so I’ll see you next week!

Myth busting the fake news about cancer research

When Hayley and I began our YouTube channel, Cancer Research Demystified, we had a clear aim in mind: to give patients & their loved ones answers to their questions about cancer research. We began with tackling the science of common treatments like chemotherapy and radiotherapy, explaining the latest hot topics in research like immunotherapy, and showing footage of what happens to a patient’s donated blood or tissue sample when we receive it in a research lab.

But over time, we noticed that these weren’t necessarily the most common questions we were actually getting from patients. Whether we were discussing latest advances in a support group meeting, consenting a patient to take part in a research study, or even just chatting to a taxi driver or barman who mentioned they had a family member with cancer – one question type was emerging as a very common trend.

Cancer conspiracies.

Now and then, patients & their loved ones would ask us if it was true that big pharma is keeping the cure to cancer a secret. Or indeed, politely inform us that this was happening, and with certainty – to them it was a fact.

While getting an Uber to my lab one day in Cold Spring Harbour Laboratory, USA, my driver told me that what I was doing was a waste of my time – that his cousin was importing the cure from China and selling it at a very reasonable price, and that the US regulators refuse to approve it, because they make too much money from chemotherapy.

In trying to engage with the online cancer patient support community, I joined a wide range of Facebook cancer support groups early on in the Cancer Research Demystified days. I was baffled at the sheer volume of misinformation being shared there. It seemed every time I logged in I came across someone trying to make money off desperate cancer patients – whether it was essential oils, CBD products or alkaline water, the list goes on.

It enraged me to see people trying to make a quick buck off vulnerable people. A cancer diagnosis is an extremely overwhelming thing, with patients getting a huge amount of technical jargon thrown at them during a time of great emotional challenge. You can’t be expected to get a PhD or MD overnight, in order to tell apart the clinicians from the scam artists, and you shouldn’t have to.

Of course the moment you bring up this topic in an office full of cancer researchers – you get a response. Everyone had their story to tell, whether it was a vulnerable relative being lead to believe they could avoid surgery for their cancer and just get acupuncture instead, or a set of memes or viral tweets convincing people that cancer researchers like us are keeping a cure a secret in order to line our own pockets.

It didn’t take long for us to decide to make a small series about this for YouTube. We roped in a colleague, Ben Simpson, who had a penchant for schooling those who were attempting to spread misinformation online. And so far, we’ve produced three episodes, under our series ‘Spam Filter’. The aim is to address these sorts of questions by reviewing the peer reviewed literature on each topic, explain the facts, and discuss why some of these rumours or myths might have managed to take hold.

Is cannabis a cure for cancer?

This topic is persistent online, and it’s easy to understand how it has grown legs, given some of the chemicals found in cannabis can genuinely help to relieve some symptoms/side effects of cancer or cancer treatment. It is not, however, a cure.

Are big pharma covering up the cure to cancer?

This one is a bit irritating to us to say the least, given we have all dedicated our lives to researching cancer. It’s also hard to provide peer reviewed data on something that isn’t real, but we’ve done our best to explain the reality of just how hard it would be to cover up a cure, given the numbers involved – as well as why nobody would bother, given they’d become rich beyond their wildest dreams by just marketing the cure instead!

Finally, the alkaline diet

This is a persistent myth online, that making you body more alkaline by eating alkaline foods (which in some case are actually acidic) could prevent or cure cancer. It’s a trendy diet, that really doesn’t make much sense at all. However, it’s very easy to see why people might think it is working, given they can test differences in their urine’s pH, that make it seem like something is changing. For this video we did some urine and blood tests on Ben, before, during and after a day of eating this diet, and discussed the facts and myths involved.

Which cancer myth do you think we should bust next? Or better yet, is there a rumour, trend or theory going around that you’ve seen, and you can’t tell whether it’s legit or not? Let us know and we’ll try our best to get to the bottom of it!

Can cancer research be done from home?

Naturally, when the COVID-19 lockdowns began, our laboratory based research had to take a pause, and we had to stay at home.

Is it possible to work from home as a scientist?

Yes!

I made this video a couple of weeks into lockdown, where I explained that there is still plenty of science that can be done without a lab. I also promised to check in later with how things went, so I’ll do that here now!

It’s now about five months later, and things have largely stayed the same…

Pubs and restaurants have reopened but I haven’t ventured into one just yet. I’m still going out for walks, and almost always wearing a mask, even in open spaces (except during the occasional isolated picnic!)

A few weeks ago, our labs began to reopen, but at very limited capacity. I haven’t been back yet – I am leaving the space to those that need it most – the final year PhD students!

I have repeatedly found myself thanking my lucky stars that I am not trying to finish a PhD this year. For those of you that are, I am thinking of you, and if there is any way that I can help you, please let me know!

I have been busy preparing for the upcoming semester, when I’ll be delivering teaching online to our undergraduate and postgraduate students. Being a module lead is a new experience for me, so leading not one, not two, but THREE modules and adapting them for online learning is going to be quite a challenge! I am so lucky that the rest of our teaching staff have been so accommodating and helpful in showing me the ropes. I hope the students enjoy my modules…

Research still ticks along, with some data getting analysed, some thesis projects getting written up, and some papers getting published, but still no laboratory work.

My current plan is to focus on honing my teaching skills, writing and project planning this semester, and then if all goes well, get stuck back into some lab work in the new year, hopefully with some new students alongside me!

Time will tell whether this goes to plan or not!