Background

42,886. This is the number of new bowel cancer cases in the UK every single year. One would think that the immense advancements in healthcare and the eradication of a plethora of diseases through vaccination would have also led to the “cancer cure.” While this sounds idealistic to the ears of a scientist, aware of the complexity of cancer as well as its heterogeneity across and within cancer types, treating and preventing cancer has seen major improvements in the last few decades. While in the 1970s, only a fifth of people diagnosed with bowel cancer survived their disease beyond ten years, now this has reached almost 6 in 10.

But how do we improve these statistics? How do we decrease cancer occurrence and how do we increase treatment efficiency? Maybe we need to move away from a “one drug treats all” and direct research to the new kid in the block; precision medicine. Understanding the complexity of our genome and sequencing our DNAs, has led us to realize that certain individuals might be more susceptible to certain disorders and more responsive to certain drugs. So how do we go on about discovering, understanding, and applying these genetic characteristics to cancer treatments?

Personalized treatment

Dr. Vidya Rajasekaran-Sutherland (Credit: Institute of Genetics and Cancer)

Many individuals have devoted their research in characterizing and studying loci in the genome called eQTLs and SNPs that are associated with one’s predisposition and vulnerability to certain diseases.  is one of those scientists currently focusing on studying eQTLs associated with colon cancer, that are found in a large percentage of the population and particularly within families. Interestingly, the research group that she is a part of at the Edinburgh Cancer Centre has come across an X-chromosome associated eQTL that results in lower expression of the gene it is found within and renders mouse males more prone to  developing rectal adenomas. This is not surprising, as hormones and the X inactivation phenomenon means that cells and tissues across the body will show a heterogeneity with many of them expressing the wild-type allele rather than the null allele with the eQTL of interest in homozygous and heterozygous females. Extrapolation of this concept to humans is indeed possible as recent study of human samples in the lab she is a member of, indicated a similar pattern.

The implications of this concept are immense according to Dr. Vidya Rajasekaran-Sutherland, and it is hard to disagree. Starting with treatment-what if we could establish therapies based on overexpressing this gene of interest in males? Not surprisingly, 56% of UK CRC cases are in males meaning that this eQTL could provide one of the answers as to why this is the case but also provide a possible drug treatment strategy. Of course, cancer is a complex disease and the temporal dynamics of when these treatments would be effective and whether other SNPs and eQTLs in the genome would affect the efficiency of therapies still remains unknown. Regardless of the ocean of unanswered questions, these small but important steps forward are very encouraging.

Personalised prophylaxis

While listening to a professional explain all the ways that we could tailor treatment and discover new strategies based on someone’s genome, a quote by Professor Michael P.Snyder came to mind: “The biggest barrier is ‘who pays?’ Our system right now is not incentivized to keep people healthy but rather treat them once they get sick.” And maybe he is right-what if we use the power that genomics offer us to attempt and decrease colon cancer occurrence than only focus on improving treatment? I was happy to see that Dr. Rajasekaran-Sutherland agreed. According to her, there are groups of individuals who could respond very well to prophylactic treatment if they have the necessary SNPs in their genome. And of course, this is significant from a financial perspective as well. If individuals are treated prophylactically, then this could remove a big part of the health system treatment costs whose duration is uncertain when it comes to cancer.  However, if we tailor one’s healthcare on their genome wouldn’t this significantly increase the costs of having so many different strategies? As Vidya explained, while tailored treatment takes ones genome into consideration the resulting strategies would most likely target groups of individuals within a population rather than just a single individual. Groups that share the same SNPs and eQTLs that research associates with drug response or disease susceptibility.

So is precision medicine the epitome of personalized healthcare? Will it be the solution to treating all conditions with an underlying genetic cause? Possibly. But we still have a long way to go. In the same way that next generation sequencing has permitted the quick and cheap sequencing of human genomes and has provided us with the necessary knowledge to study these eQTLs, the next wave of technological novelty could help us move one step further in the right direction. But we shouldn’t forget that advancements in healthcare do not only depend on science; they depend on what society deems ethical. Hence while spending most of our time as scientists trying to interpret data and find significant statistical associations, we should also consider how this research will be perceived by society and how this will dictate its applications.

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