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Genomic Innovation in relation to TCGA Network Colorectal Cancer Study

Research regarding the genome has advanced exponentially within the last decade. The price to perform a whole genome sequence (WGS) hasdecreased from $10 million in 2001 to less than$10,000 in 20121. The process itself has become more efficient, with machines that work  far more rapidly than original sequencing machines.2 Similar to other technological innovations, these advancements in genomic research will likely take decades more to be felt by the whole population by way of clinical treatment. Yet, the revolution of targeted, ¡°personalized¡±  medicine is surely coming and what that might imply for the structure of the healthcare industry is something that cannot be foreseen with certainty.

The movement towards increased usage of genomic data can be seen in a study performed by The Cancer Genome Atlas Network (TCGA Network), which provided a comprehensive 276-sample genome database of patients who had colorectal cancer (CRC) 3. The study provides  researchers across the globe with information regarding new biological markers for CRC and with new data that identifies altered genetic  pathways that may be contributing factors to tumor development. The data also suggests the possibility of using preexisting cancer drugs to supplement treatment of CRC based on common genetic mutations. However, there is no way to quantitatively predict the accuracy of using genome-based data to target specific genes.

Many high-profile diseases are complex and involve multiple genetic alterations and the discovery of one therapeutic strategy that will work with more than a majority of cases is unlikely. That is not to say that genomic research will not be able to improve clinical practices. In fact, translational genomic research and application of studies such as the one by the TCGA Network will eventually improve treatment of many diseases, particularly the Mendelian disorders that involve only one gene aberration. However, the ability to use drugs to treat the illness depends upon the nature of the disease and many diseases involve far more than one gene mutation.

Researchers hope that the genetic alterations can be traced back to a limited number of genetic pathways, thus streamlining treatment and decreasing the amount of drugs necessary, but there are other factors that must be taken into consideration. Family history is a one such factor that plays a large part in determining predisposition for and treatment of diseases4, as are general lifestyle choices. Specifically regarding CRC, it is unlikely that a common therapeutic strategy will be found in the near future to treat a majority of cases of the cancer. All of the genetic pathways that influence CRC development have yet to be identified and with the slow clinical implementation of genomic research, finding a functional drug therapy and implementing it is not likely to realistically occur in the near future.

However, the study produced by the TCGA Network, in conjunction with other studies, will raise valid practical points regarding the future of healthcare infrastructure. New concerns related to genomic research may include the regulation of patient privacy, the possibility of selective abortion, massive adjustments to insurance company plans, storage of genome data, government regulation of third-party genetic tests5, and hoards of additional dilemmas. If these are all solved, medicine will be able to shift towards the more ¡°personal route¡± that many desire; hopefully, ¡°personal medicine¡± means that medicine will be practiced with a greater understanding of the molecular taxonomy of a disease and treatments will be determined given the patient¡¯s genes and family history. Maximizing treatment and avoiding adverse pharmaceutical effects will be a priority during the next generation of medicine simply because it will become a standard to test patients for specific biological markers, for example to test for alterations of the WNT pathway for patients with CRC3.

Of course, clinical medicine has always been technically personal, taking into account medical history and symptoms of each patient. Yet with novel research, clinical medicine will become more precise6 as well, tackling each disease with more genetically reliable treatment strategies. That does not mean that clinical successes will increase in terms of treating complex diseases, but rather, this means that treatment decisions will be made possessing more knowledge than before. For example, the likelihood of a fatal adverse reaction to the only drug known to treat a specific disease may prompt the patient to refuse treatment. That situation may be extreme, however it does show that while current advances in medicine may not always offer better treatments, they will maximize information available to the patient should it be desired. The TCGA Network study and its extensive sequencing of 276 genomes highlight the fact that the genetic makeup of each person will one day be vital to ¡°personal¡± clinical medicine in making more efficient treatment decisions.

In order to expand general use of genome sequencing, knowledge must be shared freely by all researchers as well as clinicians. The only way to adopt scientific innovations in a practical manner is to have open channels of communication between those working directly with patients and those in the labs. Many technological breakthroughs have occurred in the nonmarket/network sector7 of the economy and that will surely be the case with genomic studies. The cost to sequence whole genomes justifies the movement towards the sharing of sequenced genomes, perhaps in a federated structure among hospitals and research institutions8. The constant competition for federal research grants hinders the cooperation that is necessary for genomic translational research. Through peer review and collaboration, research regarding specific diseases such as CRC will increase and allow drug development to be possible. If entire genomes must be sequenced and there is no available database of sequenced genomes to draw from, the likelihood that a pharmaceuticals company will pioneer and market a drug/drugs for CRC is slim. The cost-benefit analysis would be too cost-heavy to allow pharmaceuticals to justify drug development for a disease that is close to  being  an orphan disease, but is not.

Of course problems would arise, especially those related to the storage of genome data and protection of patient privacy. Current clinical record-keeping systems would not be able to handle receiving and protecting genetic information received from patients. It would be  necessary to either remodel existing clinics or establish new genomic medical clinics. Insurance companies would have to establish a mechanism to allow their consumers to perform genome sequencing. It is clear that dozens of problems will arise as genomic translational research advances.

However, as seen throughout history, innovation is spurned onward by the rise of problems. The very nature of research is to solve problems faced by populations. With the TCGA Network paper on CRC, it is clear that a new age is dawning in research. No longer are diseases defined by their anatomical origin, but rather, they are beginning to be defined by their molecular origins. Disease prevention and treatment will begin to adopt this new mindset and it is up to the public to catalyze the widespread introduction of genomic translational research into the clinic.

Bibliography___________________________________________________________________________

1. K. A. Wetterstrand, DNA sequencing costs: Data from the NHGRI Genome Sequencing Program (GSP); http://www.genome.gov/sequencingcosts.

2. E. S. Lander, Initial impact of the sequencing of the human genome. Nature 470, 187¨C197 (2011).

3. The Cancer Genome Atlas Network ¡°Comprehensive molecular characterization of human colon and rectal cancer.¡± Nature 19 July 2012.

4. S. Mallal, E. Phillips, G. Carosi, J. M. Molina, C. Workman, J. Tomazic, E. Jägel-Guedes, S. Rugina, O. Kozyrev, J. F. Cid, P. Hay, D. Nolan, S. Hughes, A. Hughes, S. Ryan, N. Fitch, D. Thorborn, A. Benbow; PREDICT-1 Study Team, HLA-B*5701 screening for hypersensitivity to abacavir. N. Engl. J. Med. 358, 568¨C579 (2008).

5. J. McCarthy, H. McLeod, G. Ginsburg. ¡°Genomic Medicine: A Decade of Successes, Challenges, and Opportunities.¡± Science Translational Medicine 12 June 2013: 10.

6. Christensen, Clayton, Grossman Jerome, and Hwang, Jason. The Innovator¡¯s Prescription: A Disruptive Solution for Healthcare. McGraw-Hill, 2009.

7. Johnson, Steven. Where Good Ideas Come From: The Natural History of Innovation. New York: Riverhead, 2010.

8. H. Jacob, K. Abrams, D. Bick, K. Brodie, D. Dimmock, M. Farrell, J. Geurts, J. Harris, D. Helbling, B. Joers, R. Kliegman, G. Kowalski, J. Lazar, D. Margolis, P. North, J. Northup, A. Roquemore-Goins, G. Scharer, M. Shimoyama, K. Strong, B. Taylor, S. Tsaih, M. Tschannen, R. Veith, J. Wendt-Andrae, B. Wilk, E. Worthey. ¡°Genomics in Clinical Practice: Lessons from the Front Lines.¡± Science Translations Medicine 17 July 2013.

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