Who and why?
Our kit aims to test for colon cancer in individuals who are at risk of developing colon cancer though family history, genetic dispositions or other risk factors. Another particular need for a cheap, self-test would be to help health care systems cope with the increasing burden of COVID-19, as well as providing individuals who are struggling to get in contact with health care professionals for a test due to the hospital restriction and appointment difficulties being experienced by countless individuals in the UK.
The impact and onset of colon cancer is incredibly damaging and rapid -we aim to provide a quick and accurate diagnosis which will help to progress treatment quicker to improve quality of life for individuals who often are diagnosed late, which vastly reduces life expectancy and causes significantly distressing symptoms. If we could provide a test to give individuals a second chance of treatment at an earlier stage, and helping those before they develop significant symptoms, it would be worthwhile, something we endeavour to do for the countless individuals who will suffer through terrible the symptoms as they become diagnosed this year.
The people who we ideally aim to screen would theoretically be the same people screened under the current system in the UK- people who are at least 55 years old - however ,with recent research stating that small animal pets could be a reservoir for colibactin-producing E. coli, screening could also be extended to animals to make sure that their owners do not accidentally contaminate themselves, preventing some cases of cancer.
The testing kit
Our testing kit would ideally take the form of a cell-free extract containing the engineered biosensor bound to GFP-encoding plasmids, alongside the necessary substrate for transcription and translation. This would circumvent the problem of contamination as no live cells will reach the end users.
The use of this testing kit would simply amount to taking a stool sample, adding the extract to it and waiting around 20 minutes to allow transcription and translation to occur, after which the sample would be exposed to blue light and checked for fluorescence. If fluorescence is present, the sample is positive, and there is a risk of colon cancer which can then be taken up further with a health care practitioner, allowing for an immediate treatment plan to be developed, giving the individual a stronger chance of overcoming cancer as it has been shown that early diagnosis provides the largest chance to preserve the quality of life and overcome the disease.
We want to build on the current screening methods and treatment methods, which do not discriminate between the types of disturbance present in the colon (e.g. between adenoma and cancer). The major difference in our project would be that our method would actually detect the presence of clb+ strains, which allows for better targeting of the cause of disease as well as earlier diagnosis.
In certain cases, pre-emptive measures can even be taken (for example, antibiotic treatment followed by prebiotics and probiotics to restore the gut flora which is a common practice all over the world to improve gut health, thus avoiding the development of cancer altogether. This is an incredible thing to even envision, and we are positive that this is the necessary method of treating colon cancer - by preventing it from developing in the first place! Moreover, with recent research stating that small mammal pets could be a reservoir for colibactin-producing E. coli, screening could also be extended to animals to make sure that their owners do not accidentally contaminate themselves, preventing even more cases.
As with all diagnosis tools, the psychological impact of a positive result must be considered - some screening patients may misunderstand the presence of pks+ E. coli as a cancer diagnosis despite this not always being the case; this has the risk of causing unwarranted distress, especially in the case of a false positive. This is why special care must be taken to reduce the latter to a minimum while making sure that the patient understands the link between colibactin-producing E.coli and the occurrence of CRC via information and awareness campaigns.
The bigger picture
Our initial idea for the implementation of the testing kit was such that it could be used by anyone at home providing an easy, rapid and accurate way of checking for colibactin, however as we developed our project, it became apparent that this would not be feasible - a fluorescence test requires the input of medical professionals which would limit the scope of our project- instead, we would propose that our testing kit be used as a component of a larger set of self-tests which would be able to narrow down the exact cause of each particular case of bowel cancer in case of a possible result, in order to facilitate treatment and possibly avoiding resurgences.
Moreover, taking fluorescence readings from samples could easily be automated to eliminate the possibility of human error, and with large-scale maintenance of cultures being relatively cheap, many more testing kits could be manufactured for the same cost. This would provide a streamline process with a rapid output which would benefit countless individuals.
We recognise however, there are problems with self tests -such as a individuals seeing false fluorescence, similar to false pregnancy tests, and from people naturally having higher concentrations of colibactin in their gut flora, however we aim to consult with more experts to tackle these issues but unfortunately, these issues were outside of the scope we took for our project.
- Fabian, N. J., Mannion, A. J., Feng, Y., Madden, C. M., Fox, J. G., Intestinal colonization of genotoxic Escherichia coli strains encoding colibactin and cytotoxic necrotizing factor in small mammal pets, Vet. Microbiol., 2020, doi: https://doi.org/10.1016/j.vetmic.2019.108506