Having looked at examples of some of the shockingly poor cancer research reports from the past month, let’s balance it out with some good stories shall we?

Awesome Study #1: 21 More Clues towards the Origins of Cancer

A huge study undertaken by the Wellcome Sanger Institute looked into a massive 4,938,362 mutations from 7,042 cancers, from which a total of 21 distinct mutational signatures were discovered. Put simply, these 21 signatures were found across 30 representative types of cancer.

The signatures themselves comprise of specific arrangements of DNA mutations characterised by the researchers themselves. Each signature may consist of a series of DNA deletions, insertions, inversions or many other possible configurations. Some signatures were found to be in a state of “kataegis” where numerous mutations are found in a specific place in the genome.

Some of the signatures were found across many cancers, for example, signature 1B was found in ~61% of all of the samples in the study. On the other hand, some were found in only a few cancers, such as signature 14, which was found in 0.1% of all samples. For the less common mutations, cause was not found and remain unknown. However, for the signatures that were in high numbers, causes could be attributed with further analysis in to what mutations they were comprised of. 

Cancer signatures

In order to clarify the findings, here’s a graph they presented in their study. Bear with me on this one, it took me a while to understand this too…

First of all, looking at signature 1B (yellow box), you can see that it was identified in 19 of all 30 (~61%) cancer types. Looking to the right of the graph, you can see the probable causes of these mutations (red box). In the case of 1B, age was most likely to be associated with the signature. At this point, that doesn’t seem too helpful because we know that cancer is a disease associated with ageing.

Now look at signature 3 (blue box). In this case, the signature was only found in 9.9% of all cancer types. “Why is that important?” you may ask. Well, when you look at the probable cause of the signature, you find that BRCA1 and 2 mutations may well be the driving force. Here’s a previous post indicating the role of BRCA mutations in breast cancer.

THIS is when it gets exciting (/complicated). If you know there are mutations in a specific gene then you can theoretically target that gene using therapy. BRCA1/2 mutations are common in breast cancers so therefore BRCA1/2 treatments may be more successful than conventional breast cancer therapy. Even more exciting is when specific signatures are found in few numbers in the same cancer. For example, signatures 1B and 2 are the only two that were found in acute lymphoblastic leukaemia (ALL). This whittles the gene mutations down a lot and means more specific treatment could be given in cases of ALL. On the other hand, those cancers with a variety of signatures, such as stomach or uterine, need to be investigated further into to determine which signature is best to target.

Take a deep breath. You made it.

Treating the Future

So we have 21 signatures identified across 30 cancers. We now can investigate which signatures to target to treat the disease most effectively. We could also investigate whether a treatment for one signature could apply across all the cancers it was involved in. It allows us to personalise cancer treatment even further. Instead of giving one treatment to all and hoping it works, we can now assess the probability of a cancer having a specific signature and treat that instead. It also allows for preventative actions to be taken for the probable causes we know of. For those we don’t, there’s still a bit to do. However, that’s definitely the potential of this kind of study. Pretty amazing right?

It kind of reminds me of the genome project and how the mapping of all genomic data could introduce new waves of treatment, the likes of which the world had never seen! But instead of confusing everyone with a vast amount of information like the genome project, this study is a much more refined picture, albeit with more work to be done. It’s a defining moment in cancer research that may well change the way we think and treat the disease.

Awesome Study #2: Time for Something Lighter…A Gene Gun Perhaps?

Just look at that thing. It’s like something fresh from Star Trek…

Moving away from the rather daunting genetics side of cancer, let’s take a look at something new – a “gene gun“. Although the technology is not new (it has been used for years as a way of introducing genes into plant material), the idea of treating cancer with one in this way is.

In a much smaller study than the previous one, a gene gun was used to deliver an anti-cancer drug directly into cancer cells. The drug in question was mitoxantrone dihydrochloride (MTX), a therapeutic that has proven very effective against metastatic breast cancer. The drug was delivered using non-conventional, biodegradable porous silicone (PSi) carriers (instead of the usual heavy metal nanoparticles). The PSi-MTX particles were fired into in vitro cancer cell samples to test the efficiency of the system.

Seems pretty simple right? Well that’s the beauty of it. The system was found to work incredibly efficiently, killing the majority of cancer cells within 120 hours post-treatment. In order to determine whether the cells were dying of physical trauma rather than the drug, cells were also bombarded using “naked” PSi particles, without a drug attached. The results concluded that almost 100% of the cells survived when exposed to the particles alone. 

So the gene gun is delivering the drug directly into cancer cells – using particles that aren’t harmful on their own – and when it does, it has a very high efficiency of killing them.

The study went on further to see if the particles could withstand a physical barrier. This time a piece of porcine (pig) skin was placed beneath the gun barrel and a sheet of gel. The results proved that the particles were able to pierce the skin barrier highly efficiently, delivering a significant amount of the drug.

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The gene gun arrangement, showing the use of porcine skin as a human skin emulator. The PSi-MTX particles were shown to penetrate the relatively thick skin very efficiently.

…So Why Is This a Good Thing?

Think about it this way – if there is a solid tumour (i.e. a large tumour mass) that you would like to treat specifically, without damaging surrounding tissue, with a very high targeting and drug delivery efficiency, then this may well solve your issue. The problem with targeting solid tumours is that most treatments find it difficult to reach beneath the surface of a tumour (this is particularly evident with antibody therapies) whereas this system is able to deeply penetrate tissue.

Also to consider is the variability of this kind of potential treatment. The particles can be conjugated with many anticancer drugs currently available, therefore most cancer cells could be honed in on using the drugs we know are effective against them. The particles can be manipulated to release drugs over certain periods of time, meaning you can control drug release into the tissue. The gun itself can be fine-tuned to penetrate deeper into tissues and the diameter of the barrel can be adjusted to produce a wider spread of particle administration.

It’s a very sci-fi-esque way of treating cancer by combining nanotechnology with conventional cancer treatment and it’s not exactly mainstream and it’s a very specific way of treating it, but exciting all the same. Obvious questions as to how the drug can be administered into tumours far beneath the skin’s surface haven’t been answered in this study but, for the time being, the system presents an effective means of highly targeted therapy.

A Month in Summary

All in all, it’s been a pretty mixed month for cancer research, but then that’s what it’s like almost every month. There’s always an example of poor reporting represented in the media that uses stories that aren’t actually that exciting. And because of that, people get the wrong impression of it as trying to strike fear into the general public with a painfully repetitive view of just about everything under the sun being able to cause cancer. It’s when you start researching into it further that you begin to find the interesting stuff. These are just a couple of examples of the extortionate amount of research constantly being published.

I hope this two-part post has brought attention to just how easily data can be misused but also to the exciting developments of our time.

Read more:

The genetic signatures study: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12477.html

The gene gun study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3752615/

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