Chemotherapy, the full story

Very few treatments cause as many side effects as chemotherapy does, especially when taken the treatment’s fullest extreme. Many advocates for alternative medicine have strong opinions against the use of the drug, claiming that it does more harm than good, making the treatment controversial in some areas of science. In many cases, chemotherapy is used as a supplement to additional treatments such as surgery or radiation. However, patients diagnosed with hematological malignancies such as leukemia and lymphoma, must go through extensive chemotherapy treatment because their form of cancer is not concentrated in one area, such as the breast tissue or brain, so surgery is not a viable treatment (Gorski 2013).

Chemotherapy is infamous for its long list of side effects which include: hair loss, nausea, fatigue, loss of cognitive function, reproductive issues, and permanent damage to the heart, lungs, kidneys, or reproductive systems (cancer.net 2015). A clinical trial performed by Dr. Karolina Tezca (2015), demonstrated that cytotoxic drugs are meant for the destruction of cancer cells. However, these drugs are simultaneously destroying healthy cells or tissues with high growth rates that happen to get in their way, such as epithelia in gastrointestinal track and cells located in bone marrow and skin. Joe Simpson of Camberley was diagnosed with pancreatic cancer in 2008 when he was only 27 years old. During treatment Joe wouldn’t get out of bed for weeks on end, he was in too much pain and too weak to walk up the stairs, and developed such severe depression he refused to speak to anyone (Simpson 2008). Sometimes it can be hard to decipher what symptoms are related to chemotherapy treatment or due to cancer, but regardless there needs to be a better way to relieve millions of people every year from the physical and emotional burden that comes along with the dreaded three words: “You have cancer.”

According to the American Cancer Society (2016), the overall mortality rate of diagnosed individuals under fifty years of age has steadily declined by 2.6% per year since 1986, nonetheless over half a million people in the US are estimated to die of cancer this year. In many cases chemotherapy saves lives. It decreases the risk of dying from breast cancer by one third in diagnosed individuals (Gorski 2013). It is also true that chemo can’t save every patient. For people who are diagnosed too late, chemo isn’t effective or causes related toxicities. Actually finding the problem before it becomes one will make the difference.

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Cancer without a poker face

Chances are most people know someone who has been diagnosed with cancer. According to the American Cancer Society (2016) approximately 39% of the population will be diagnosed with cancer at some point in their lifetime. In the late 1500’s, influenza had a detrimental effect on much of Europe, wiping out several Spanish cities. Now, imagine the 21st century obtaining the capability to treat cancer with as much as ease as the common flu, a once deadly disease.

The National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) launched a project in 2006 to characterize the genomic and molecular components of cancer named The Cancer Genome Atlas (TCGA). This database includes over 10,000 primary tumors over 33 cancer types all sequenced for mutation detection, as demonstrated in Table 1 (Weisenberger 2014). TCGA was created to become a useful resource for researchers to reshape cancer treatment strategies. Cancer genomics is advancing personalized medicine through sequencing and exploration of malignant growth. Each tumor has its own set of genetic  adaptations and understanding these  changes are what tailors to a more specific treatment plan specific to the genetic profile of each patient’s diagnosis (National Cancer Institute 2016).

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Table 1: Tumors selected by TCGA for genomic sequencing, http://www.tega-data.nci.nih.gov

Genome sequencing is the decoding of the all the genetic material in one organism. Just the code, however, does not give much insight as to what it means. Each string of letters must be translated into an understood, universal language that explains how each gene is related and how each part of the genome coordinates to one another (Genome News Network 2003). To decode a genome, it is split into parts, put back together, and analyzed as if it were a puzzle. According to the Genome News Network (2003), there are two ways to dissect a genome. The first approach is the “clone-by-clone” approach which involves breaking the genome into large chunks, called clones. Scientists then figure out where each clone belongs in the genome, sequence each piece, and use overlaps to decipher the entire clone. The other strategy is called “whole-genome shotgun.” The genome is cut into many small pieces, sequenced, and reassembled (Genome News Network 2003). This method is considerably faster, although it is more difficult to piece together many small genome segments.

According to Dr. Neil Hayes, of the University of North Carolina- Chapel Hill, and co-principal investigator of the TCGA project, “TCGA was the project that needed to be done; there had to be a large scale profiling of tumors to figure out the genetics of cancer,” (National Cancer Institute 2016). Knowing more about tumors gives insight on their location and how to target them for treatment. Providing researchers with defining characteristics of genomic changes, in specifically subtypes of cancer, will support revolutionary advances in ways of diagnoses, treatment, and prevention.

UNC CH is Working On New Treatments

Dr. Charles Perou and his team of researchers at the University of North Carolina- Chapel Hill are digging into TCGA towards more effective cancer treatments. One of his colleagues, Dr. Michael Gatza, is finding common themes in cancer development through studies of the collaborative genome sequence and analysis. He presents potential targets for treatment drugs that were once unknown “to create an approach to identify genes that were not only implicated in the growth of breast cancer but that were also essential for cancer cells to  survive” (Resnick 2014). Subtypes of cancer can have limited treatment options, such as luminal breast cancer, which often have mutations within similar genes between patients, however the many differences in its diagnosis make it very difficult to treat (Resnick 2014). At the top of Figure 1, different subtypes of breast cancer are separated into columns and on the right side of the figure, the names of all the pathways Dr. Gaza analyzed. Each red mark indicates upregulation of the pathway while a blue mark indicates downregulation. Different subtypes use different pathways, however the subtypes recorded here are similar within subtypes (Resnick 2014). Dr. Gatza found that this cancer consistently works on the same cancer pathways, creating observable targets for specialized treatment.

 

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Figure 1: Genomic sequencing of subtypes of breast cancer, Figure 1a Gatza, M.L.

With this new research, genes can become targets for new treatments “using genetic techniques to turn off these genes causing the luminal cancer cells to die” (Resnick 2014). This research has the potential to revolutionize cancer treatment. People like Joe Simpson could walk away from a diagnosis with a clear and optimistic treatment plan, one where they can continue to live a life with a head full of hair and future ahead of them.

Bibliography

Cancer facts & figures 2016. American Cancer Society, Inc.; 2016. Report nr 500816.

Genome Sequencing [Internet]: Genome News Network; c2003 [cited 2016 September 28]. Available from:  http://www.genomenewsnetwork.org/resources/whats_a_genome/Chp2_1.shtml.

Gorski D. Chemotherapy doesn’t work? not so fast. [revised October 28, 2013;cited September 18, 2016]Science-Based Medicine. Available from https://www.sciencebasedmedicine.org/chemotherapy-doesnt-work-not-so-fast-a-lesson-from-history/.

My Husband’s Chemotherapy Story [Internet]: Cancer Research UK; c2008 [cited 2016 September 23]. Available from:  http://www.cancerresearchuk.org/about-cancer/coping-with-cancer/tips/emotionally/my-husbands-chemotherapy-story .

Resnick S. From chemo to genome A step towards personalized cancer treatment. Carolina Scientific 2014;7(1):12-3.

Side Effects of Chemotherapy [Internet]: Cancer.Net; c2015 23 September 2016]. Available from:  http://www.cancer.net/navigating-cancer-care/how-cancer-treated/chemotherapy/side-effects-chemotherapy.

Tecza K. Pharmacogenetics of FAC chemotherapy side effects in breast cancer patients. Hereditary Cancer in Clinical Practice [Internet]. [revised 2015 26 November 2015;13(2): 30 August 2016-A10. Available from http://vb3lk7eb4t.search.serialssolutions.com/?

The Cancer Genome Atlas (TCGA): The next stage [Internet]: National Cancer Institute; c2016 25 September 2016]. Available from:  http://cancergenome.nih.gov/newsevents/newsannouncements/TCGA_The_Next_Stage.

Weisenberger D. Characterizing DNA methylation alterations from the cancer genome atlas. The Journal of Clinical Investigation [Internet]. [revised 2014 2 January 2014;124(1):30 August 2016,17-23. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3871233/?tool=pmcentrez.