Although cancer research is predominantly thought of as improving current treatment regimes, another aspect of the field is that of screening for the disease. Screening for cancer is just as important as improving our treatments, something which many of us forget due to mainstream media mainly focusing on the latest cancer killer. However, without screening, effectively treating cancer would be virtually impossible. 

Testing the Waters

The biggest news this month in terms of screening comes in the form of a Cancer Research funded project investigating bladder cancer. The study claims that epithelial cell adhesion molecule (EpCAM) can be measured from urine samples to determine the stage of bladder cancer.

Positive Feedback Is Not Always a Good Thing…

The major role for EpCAM is to anchor one epithelial cell to another, usually in an adjacent manner, however it also governs many other reactions within normal epithelium. For example, one study has pin-pointed the protein as being responsible for causing “positive feedback” reactions – the presence of one protein initiating the production of another. Reactions that can lead to very serious issues when not properly regulated…

epcam_cancer
The extracellular domain of EpCAM can interact with further proteins to encourage even more EpCAM cleaving – this is referred to as a “positive feedback” reaction. The intracellular domain can encourage cell proliferation and survival through interaction with DNA sequences.

The cleaving of a complete EpCAM protein into an extracellular domain (outside of the cell) and an intracellular domain (inside the cell) leads to the activation of some major positive feedback reactions. Firstly, the presence of extracellular EpCAM can actually trigger further cleaving of more EpCAM molecules, causing a mass ‘shedding’ behaviour seen in some tumours. Secondly, the intracellular domain can interact indirectly with some major oncogenic DNA promoters including c-myc – a prominent promoter of cell survival and proliferation.

Now, presumably in normal circumstances, the cleaving of this EpCAM would cause a reaction in which cells migrate to an area of trauma, causing a huge array of chain reactions leading its healing – the interaction with cell proliferation promoters would suggest this type of function. In many cases of cancer, the tight regulation of cell division tends to have become nonsensical, leaving cells in the impossible task of healing damage that is not actually present, hence the reason that cancer is often referred to as “a wound that never heals”.

How Does This Indicate Bladder Cancer?

Having EpCAM promote its own cleaving which in turn promotes extensive cell proliferation, has some serious potential toward oncogenic promotion, especially if the cell is not properly regulated. This is exactly why EpCAM is regarded as a serious potential therapeutic target in future cancer medicine. In this latest study of screening for bladder cancer, ELISA testing was performed in order to establish levels of EpCAM in urine samples from 607 primary cancer sufferers and 53 non-cancer controls. Results suggested that the level of extracellular EpCAM coincides with the presence of bladder cancer.

For the moment, this seems like good news. To find a biomarker of cancer that can easily be tested for in an cheap, non-invasive and accurate fashion is what cancer research is yearning for. Currently the method has not been tested for relation to urinary tract or general infection so the results here have to be taken with a pinch of salt. It is definitely good news and could well develop into a front-line procedure or perhaps influence a better, more definite version.

It was when reading this study that I decided to investigate further into cancer screening methods. After all, the only cancer research screening news that has been hugely prominent for the past few years was regarding breast cancer screening. Something which, in my opinion, is ridiculous when you consider how vital screening procedures are to the effective management of many cancers. It was when traipsing through numerous articles than I found the following story that, incredibly, garnered very little attention…

Pancreatic Cancer Cured by a… Teenager?

I don’t know about you but when I was a teenager, I was mainly concerned with the various troubles that come with growing into a man. When you hear news that an effective cancer screening method was invented by a (at the time) 15-year-old student, you can’t help but be pretty astonished.

In July this year, a video was posted from a TED conference in California exhibiting one of the most promising concepts for cancer screening the world has ever seen. The talk was conducted by Jack Andraka, someone who decided to make a difference in the light of his uncle’s death from pancreatic cancer. During the incredible talk, Jack revealed his invention to the world: a screening tool made from paper, single-walled carbon nanotubes and antibodies – a method that is incredibly cheap, easy to construct and non-invasive. And most importantly, identifies the signs of pancreatic cancer at its earliest stages.

The concept is simplified in his talk, mentioning how tumour protein-specific antibodies can be attached to carbon nanotubes which can then be mounted onto the surface of paper. This paper can then be dipped into a fluid sample to determine the presence of a particular protein that is over-expressed in the majority of pancreatic cancers (in this case. mesothelin). So far the method has been tested in preliminary blind studies, revealing an accuracy of 100% whilst exhibiting an increased sensitivity over existing screening methods of over 200%.

Long-term Potential

Pancreatic cancer is renowned for it’s elusiveness during the early stages of disease progression, only exhibiting symptoms at a very late stage. Because of this, the survival rates for the disease are abysmally low, with over 85% of all pancreatic tumors presenting in their most lethal form. Even so, up to 30% of all pancreatic cancers can be missed due to present poor screening procedures for the disease. Because of these statistics, there is an overwhelming sensation that progression in pancreatic cancer treatment has been left behind whilst others are rapidly improving, for example in breast and testicular cancer. Perhaps with Jack’s invention, this perception can be turned completely upside-down, especially when considering the potential of the method.

Pancreatic Cancer Survival Statistics
The five-year survival rates by age in the UK between 2005 and 2009. The picture is a sorry sight and unfortunately reflects very similar statistics all over the world.

The core principle behind the concept is the use of a protein specific antibody that selectively binds to mesothelin. In pancreatic cancer, mesothelin is abundant in very high levels in the body. So far this sounds perfect. Well here’s some more to think about: what about if those antibodies were targeted towards another protein? Then screening can be performed for other cancers that also exhibit tumour-specific proteins in bodily fluids (prostate specific antigen for example in prostate cancer). Furthermore, there’s potential for different diseases, different viral, or even different bacterial infections, to be tested for using the same method. All that needs to be changed is the specificity of the antibodies attached the the carbon nanotubes. The list is seemingly endless.

Or is it? Well when it comes to producing protein specific antibodies, it’s never quite that easy to produce a perfectly working example. There are many considerations involving the binding site (where the antibody actually attaches to the protein), the affinity of the antibody (how well it binds to the target protein), the stability of the antibody, it needs to be easily manipulated; you get the picture. Considerations like these are part of the reason why many antibodies become unstuck in their preliminary stages of testing (as well as the need for some serious cash to actually proceed with your invention).

In this case however, everything seems to working exactly as it should do. Whether a test like this can be scaled up to full production remains to be seen,  but for the most part, all seems promising for the teenager. Since the unveiling of his invention, Jack has won numerous awards for his work and quite rightly so. The concept may well be developed into something that can save millions of lives throughout the world or perhaps inspire similar concepts for different diseases. Let’s hope all is as good as it seems.

Conclusion

Screening for cancer is often overlooked yet is as vital to our success in curing the disease as finding the latest effective drug. When referring to a “cure” for cancer, it shouldn’t be an image of a radical new pill that applies to everyone because, quite frankly, that’s very unlikely to happen. It is research into identifying the disease at its earliest stages that increase the effectiveness of current treatment and should be given as much spotlight as a new therapy. Effective screening may very well uncover a cure that has been staring us in the face all this time.

Read more:

The bladder cancer article: Bryan, RT et al. “Urinary EpCAM in urothelial bladder cancer patients: characterisation and evaluation of biomarker potential” (2013) British Journal of Cancer.

The TED cancer page: http://www.ted.com/topics/cancer

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