Let’s end melanoma. For good.

Apologies for the somewhat dramatic sounding title but, well, that’s pretty much the end goal of the idea I’m going to lay out below in a somewhat epic post. Hope it’s not too long…

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Apologies for the somewhat dramatic sounding title but, well, that’s pretty much the end goal of the idea I’m going to lay out below in a somewhat epic post. Hope it’s not too long…

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What if we could stop someone getting melanoma, for good. I mean, stop it happening in the first place. What if we could make it so no one would ever have to hear those words “I’m sorry – it’s melanoma”. Not wait until it happens and try and cure it, not spend years undergoing "high risk" surveillance, worrying it’s going to happen, or come back, in an attempt to catch it early – what if we could stop the cancer from ever appearing to begin with.

Somewhat incredibly, it’s looking like that “what if” may actually be possible – but it’s going to take a lot of effort from us, the community, and a heck of a push of people power if we want to make this a reality. And God knows I do.

There’s been a lot of research done over the past few decades into cancer, and specifically melanoma, but I think everyone will agree that the sad truth is, while a lot of groundwork’s been done, there’s been precious little progress made in terms of new treatments that make a real difference. We’re still seeing drugs that buy us an extra few months of time, at a cost of high five figures, or low six figures a course. And with people’s lives at stake, that’s simply not good enough. Meanwhile, countless money’s being spent on studies that simply tell us how many people are getting melanoma at the moment, and try to figure out why, leading to the same contrasting information we’ve all heard, over and over again – increasing sun exposure’s causing more people to get melanoma, yet more and more people are working indoors, and paradoxically, are therefore getting less exposure. Children aren’t going out enough to get enough exercise, and are becoming obese, yet are being exposed to too much "damaging UV" radiation, causing melanoma in their early adulthood. Makes sense, right?

Nope. It seems that a lot of the money that goes into melanoma research – and science in general – is going into the wrong places, funding studies of limited scope, or ones that don’t add anything to our understanding of the disease. And that’s the saddest part of this, as the money could do so much more. (see – http://www.nytimes.com/2009/06/28/health/research/28cancer.html?_r=1). While I don’t disagree that we need an effective treatment, and I fully agree that this needs funding – because God knows we still need a cure, and we always will – the area that stands to create the most benefit for mankind as a whole – that of prevention – has been pretty much entirely overlooked by the research community. Perhaps that’s because of the (entirely unproven) theory that the increase in melanoma is down to us lot just being stupid and going out in the sun too much – maybe, in the research community’s eyes, they seriously think the preventative measures we have are already enough – if we’d just have been that little bit more careful, “seek shade”, “wore sun protective clothing”, and stayed indoors between 10 and 4 (basically, the entire day), we’d be fine. We’d all have rickets, be flat lining in vitamin D, and never see anything of what life has to offer, but hey, we wouldn't be at risk of melanoma.

But the sad truth is, we still have no idea what pattern of sun exposure causes melanoma. We don't even know whether being “exposed” to the sun is more important when you’re a child, or an adult. And don’t get me started on how unscientific the whole epidemiological field is. I have yet to see a definition of “intermittent sun exposure” that’s consistent from study to study. Most, incredibly, don’t even attempt to define it. And how scientific is that? What does it actually mean? Isn’t *everyone’s* sun exposure intermittent, seeing as few stand outside all day, and even if they did, the sun rises and sets anyway? It’s a nonsensical term, without definition, that’s open to far too much interpretation – yet “intermittent” exposure has become established as the most important sun related risk factor.

The whole field’s full of paradoxes. In the UK, for example, the highest rates of melanoma are found in Torbay (by the sea), Plymouth (by the sea), and Oxford, which is about as far from the sea as you can get. There are no patterns, no trends, that show exactly what’s happening, and not a sausage of proof that there’s anything we can do to that will actually, 100% prevent it. The relative risks for the amount of moles you have are many times higher than those for sun exposure, so even if we did know what pattern of sun exposure caused melanoma, it likely wouldn’t make that much of a difference, as seemingly the most important risk factors are genetic. Yet all the researchers seem to be doing at the moment is shaking their heads, quietly tutting, and putting all the blame on silly old us, our holidays, and our leisure time spent outdoors.

I know, I know, not all researchers are that judgmental– and I apologise to anyone who knows a researcher who’s working diligently to find a cure, or even if you are a researcher working hard to find a cure. It seems to mostly be the epidemiologists who’re doing the patronising head shaking – but several of the most vocal (and therefore influential) seem to have taken the opinion that we bring it on ourselves – and that's shaped the efforts of the entire scientific community, meaning millions of dollars have been spent on studies looking at why people like tanning, or following the sun protective habits of huge cohorts of people, without any evidence, at all, that any of the measures being researched will actually make a difference.

We can’t afford to wait for science to figure out exactly what proportion of melanoma is genetic and environmental. We can’t afford to wait for science to figure out what exact pattern of sun exposure causes this cancer. At this rate, it’ll be decades away, if we ever figure it out, and tens of thousands will lose their lives, while hundreds of thousands will have received that scary diagnosis. We have to make science, by hook or crook, turn its attention to prevention – true prevention – so we can put an end to melanoma, once and for all.

How do we do that? Well, I’ve done a fair amount of reading on the subject over the past few weeks, and I think I’ve seen a way. Just so you don’t think this is just the rantings of some crazy guy off the internet, I’ve also been speaking to immunologists, who say I’m spot on, and share my frustrations with the overly conservative – and seemingly set to fail – path research is taking. These scientists want the change as much as we do. But the powers that be, won’t fund “risky, unproven” research – despite knowing full well that it’s the risky, unproven research that’s most likely to give us the results we need. So here’s the plan:

I’m sure everyone on this forum’s heard about the vaccines against melanoma. These currently work slightly differently to the sort of vaccines you have against TB, or measles, as they’re designed to try and cure the cancer in someone who's already got it, while the TB vaccine’s intended to prevent people from ever getting TB in the first place. By encouraging the immune system to target antigens that melanoma cells display – small proteins that effectively work like flags, telling your body if a cell's friend or foe – these vaccines hope to encourage your immune system to reject the cancer, and flush it from your system – the big advantage of a vaccine being that, much like an elephant, it never forgets, and you should have some sort of lifelong protection against any future melanomas.

The only problem is, the results of clinical trials up until now, have been somewhat disappointing. While some people have experienced great results from the vaccines (and I’m sure we have a few on this forum), in current clinical trials, vaccines have almost been set up to fail. If there’s one thing history’s taught us, it’s that vaccines are rarely, if ever, effective in the face of established disease. A vaccine against TB would barely scratch the surface if you gave it to someone who already had the disease in full swing – the same goes for almost everything it’s currently possible to vaccinate against, with very few exceptions. Had those vaccines been tested as cancer vaccines are now, we’d likely still be plagued by polio, diphtheria, typhoid, and smallpox, as the vaccines simply wouldn't have coped in the face of established disease. And as the current melanoma vaccines are being tested on people with Stage IV cancer, they appear to have an even bigger uphill struggle. In this situation, the person has usually been through chemotherapy (which weakens your immune system), and in the case of clinical trials, often have a large number of tumours that are churning out immune suppressants, all of which conspire against the vaccine. That's not to say the current approach is impossible – and I certainly hope it's eventually figured out – but Stage IV disease, with a compromised immune system isn't the best of places to test a vaccine, as there are so many things working against it. That melanoma vaccines have actually had a limited amount of a success is a testament to how powerful the technology and idea is – but we need to have a paradigm shift. We need to move vaccines from a late stage therapy, to a first line strategy that’ll stop the cancer ever developing in the first place. We need to move a clinical trial to immunise against melanoma before it even happens.

Over the past few years, a veritable quantum leap’s happened in the world of science. We’ve got to the point now where we can look at someone, and be able to tell fairly accurately how likely they are to get cancer. After that? Well, seemingly the scientists haven’t thought that far ahead, as a fair proportion (although not all) seem to be of the impression that being able to tell someone they’re at high risk of an incurable cancer, and there’s nothing they can do about it, is always, without fail, “a good thing”. Your only hope is to catch it early enough – and that relies on your cancer being a slower growing, less aggressive one. “Go out and live your life – try not to worry”. Fat chance, eh?

This isn’t good enough. Creating this mass ecosystem of anxiety, where everyone’s “at risk”, for the duration of their lives, without any way of mitigating that risk, is not on. This is where the paradigm shift comes in. Rather than trialling vaccines in a situation where eveyrthing's working against them, we need to start trialing them in a situation where the stars have all aligned in their favour. Rather than trying to cure a cancer, we need to try and stop a cancer (or a recurrence) happening in the first place. What we need to do is move vaccines into a preventative, or prophylactic setting, rather than as a treatment – and then we’ll really see what they can do.

There’s no reason why this wouldn’t work. In an established tumour, you're faced with a heterogeneous mass, made out of several populations of cells, possibly even dozens, all of which may be displaying different types of antigens. While your vaccine may train your immune system to take out one set of cells displaying that antigen, it may leave others that aren't, letting the cancer carry on growing. In the prophylactic setting, there is no heterogeneous tumour to target. There’s no variation, no immune suppression, no edited tumour. In a healthy person, all your immune system would have to do is find that tiny cell, or cluster of cells, and wipe it out before it can even gain a foothold.

This is a plausible future. Imagine a future where our children, and our children’s children wouldn’t have to be followed by a dermatologist for the rest of their lives. Where they wouldn’t have to go through countless biopsies, scares, anxiety, and possibly even cancer treatment themselves. Imagine a world where “wide local excision” can disappear from our lexicon forever.

This is possible. The science *is* there. Even five years ago, if I’d have said you could use a vaccine to stop you ever getting a cancer in the first place, you’d have looked at me like I was crazy, but this isn’t science fiction. This is happening now.

The place where research like this is gaining the most traction, as ever, is breast cancer, as it’s the most fully funded. The National Breast Cancer Coalition in the US has announced the Breast Cancer 2020 Deadline to develop a preventative breast cancer vaccine. If this is a success (and by God, I hope it will be), this could, and should open the research floodgates. Even if it doesn’t, their structured, by the numbers approach should tell us so much more about immunology, and how the immune system responds to cancer, along with the sort of antigens we should be targeting that it should push the field forward at an astounding rate. In Pennsylvania, Dr. Czerniecki has achieved stunning results against DCIS – an early, non-invasive form of breast cancer that’s analogous to melanoma in situ http://www.uphs.upenn.edu/news/News_Releases/2012/01/cancer-tumors/. After being injected with his vaccine – arguably a more complex version than I’d like to see, as it involves taking your own blood cells, modifying them, and injecting them back in, although apparently he does intend on simplifying it – 18% of people were left with no evidence of disease through the vaccine alone, while over 50% had no evidence of the target antigen remaining, along with a large reduction in the size of their cancer. And this was in people who effectively already had cancer, with a vaccine targeting a single antigen. Perhaps when combined with numerous antigens, it’ll be more effective. There was also the highly publicised work of Dr. Tuohy (http://www.lerner.ccf.org/news/2010/5/4.php), who created a vaccine that was 100% effective in preventing breast cancer in mice. He’s now looking for funding for human trials. Perhaps he’s been interested in working with us on a vaccine for melanoma.

Regarding melanoma specifically, preventative vaccines have been successful in mice numerous times, and there are countless vaccines in various stages of trials in a therapeutic setting . We know of several antigens that are displayed only (or overexpressed, or displayed differently) by melanoma cells, and shared across the majority of melanomas. There’s also recently been a very interesting case described here – http://www.ncbi.nlm.nih.gov/pubmed/22110189. In laymen’s terms, this is a man who suffered from a melanoma, and during follow up, his body spontaneously developed an immune response against his melanocytes – which are the cells that make up moles. Over a period of weeks to months, his body attacked and destroyed the majority of his moles, without causing an auto-immune reaction like vitiligo. You’d imagine that something like this would also protect against melanoma. This is an essential proof of concept that something like this really can work – without dangerous auto-immune responses. If we take the antigens his immune system was targeting, perhaps we’ll have our preventative vaccine?

So, I hope you’re reading this now, excited about the science, and what the future may hold. But how do we make something like this happen? I wish I had a website I could point you towards to offer your help and support, but I’m afraid I don’t. For us to manage to create a vaccine that works in a preventative setting will take a lot of organisation, time on our part, and, of course, money. To try and get everyone working on the same page, I’m intending to post this on several melanoma forums, as there doesn’t seem to be an easy way to get my idea in front of everyone. Please, feel free to do the same if you also visit a melanoma forum I haven't yet posted this on. The more people who read this, the better. I’ve also e-mailed charities directly. First, I e-mailed Cancer Research UK, and sadly received an e-mail back that was confusing at best. Their Chief Clinician told me they were interested in making a vaccine for preventing a recurrence of a cancer once it’s developed and been removed (no mention of melanoma specifically) – yet Cancer Research UK currently have no projects, to my knowledge, that are even along this sort of line. All their vaccines, as far as I can tell, are still being tested in phase IV patients – not to prevent recurrences, and not to prevent it happening in the first place, where they’re most likely to succeed. And I have no idea why. As the public pay their bills, their salaries, we should have a large say in where our money goes. I’ve also emailed both the Melanoma Research Alliance, and the Melanoma Research Foundation about this (over a month ago now), but sadly, and somewhat surprisingly, I’ve received no response. I would have thought that organising, and sourcing funding for a groundbreaking project like this would be each charity’s top priority, as it could help so many people – both at risk of a first primary, and at risk of a recurrence. I’m more than a little bit disappointed that I’ve received no response from the very people who should take this most seriously. Hopefully with a bit of help from you guys, if you agree this is a good way for things to go, we can get things moving. Perhaps you guys and guyettes would like to send e-mails to the charities I've listed above, to show the demand's more than just me?

The biggest problem I can see is that there are no organisations for melanoma like the National Breast Cancer Coalition, or Komen. There’s no one big organisation with the funds to make this happen – but there are loads of smaller ones, each doing an amazing job of raising funds, but without the financial clout to be able to fund anything like this. What I’d ideally like to see is a coalition. A coming together of the charities. We’re all working towards the same goal – each and every one of us on this forum would first and foremost love to see melanoma become a thing of the past – and the most effective way to get there is if we all work together – across countries, continents, and the world. We could then, as one organisation, approach researchers with a view to finding the most cost effective, and quickest route to creating a vaccine that’s safe, efficient, and most importantly, can quickly be approved. The publicity we could raise from taking such a radical approach, a coming together of the charities, with a goal towards funding a groundbreaking preventative measure, should go a long way to helping us raise the funds. Unfortunately, this won’t be cheap. A trial, to show efficacy and safety, would cost in the region of $2m. This seems like a lot, but it’s not a figure that’s undoable. The large organisations, like Cancer Research UK, and the US NIH have already proven they aren’t willing to fund a project like this. It’s too risky for them. If we want this to happen, it’s down to us to make it happen. If we push hard enough, if we pester the public, charities, organisations, Governments for funding, we *can* do this. Australia has a very public problem with Melanoma. As do the Nordic countries, and the US. This is costing them hundreds of millions every year in treatment alone, not to mention lost productivity. It could be the best investment they’ve ever made. And we can open their eyes to that. Never underestimate what a group of people, driven by the same goal, can achieve. We can do this, if we work together.

In summary, raising awareness of a disease we still have no idea how to prevent can only get us so far. Few of the current research efforts are going far enough. We need to do better. We can do better. We need to test vaccines where they stand the best chance of working. For the sake of our children, we need to come together, stand up as one, and make the world listen, to make melanoma a thing of the past. We need a preventative measure to stop melanoma developing in the first place. And this is how we can do it.