An important development in cancer research is the use of targeted therapies. Targeted therapies target specific molecular molecules that enable the cancer to develop rapidly, unlike traditional cancer treatments such as chemotherapy and radiation which can really harm a patient’s health (in addition to cancer cells, chemotherapy and radiation often kill healthy cells). Molecular markers are like flags that reveal a target DNA sequence. Essentially, targeted therapies mount a response against specific cells, such as cancer cells, rather than all cells in a given region. Currently, there are few FDA-approved targeted therapies for colon cancer that involve molecular markers. However, there has been extensive research on the different molecular markers that allow colon cancer to grow rapidly. In particular, researchers are currently looking into therapies that target microsatellite instabilities.
A key investigation is whether microsatellite instability in our human genome (all the DNA in the body) can be used to screen for colon cancer. To clarify, a microsatellite is a short sequence of DNA that repeats throughout the genome. Microsatellite instability is a mutation (a change in a DNA sequence that can cause a wrong protein to form) in this short sequence of DNA that cannot be repaired (Boland).
Microsatellite instabilities play a relatively significant role in the development of colon cancer. In fact, about 15% of colorectal cancer cases have microsatellite instabilities (Pino). The rather prevalent appearance of microsatellite instabilities in both hereditary (passed on through family linkage) and sporadic (not passed on through family linkage) colon cancer shows that they can affect a wide range of cancer cases (Boland).
Even more so, the amount of microsatellite instabilities (low, medium, and high) can affect the development of the tumor and determine the effectiveness of a cancer treatment (Kloor). For example, patients with Lynch Syndrome, a form of colorectal cancer that consists of tumors with high levels of microsatellite instabilities, might have the ability to respond well to chemotherapy, but many studies currently state that patients with tumors with high levels of microsatellite instabilities may not need chemotherapy, due to the low levels of tumor metastasis (tumor metastasis involves tumors spreading from the origin and growing in other parts of the body). Furthermore there is indication that in patients with high levels of microsatellite instabilities, survival rates are higher when using surgery treatment alone (rather than using both surgery and chemotherapy treatment) (Kloor). Additionally, patients with stage 2 colon cancer may exhibit a higher microsatellite instability than do patients with stage 3 colon cancer (Boland). As a result, patients with stage 2 colon cancer may show a resistance to chemotherapy (Beucher). Logically, patients with stage 3 colon cancer may respond better to chemotherapy treatments.
Testing to determine whether your case of colorectal/colon cancer involves microsatellite instability and whether you have Lynch Syndrome is encouraged. In one test, pathologists take a colorectal polyp sample and a healthy cell sample, and run the samples through a process called the Polymerase Chain Reaction, which allows scientists to get large amounts of a desired DNA sequence. Polymerase Chain Reaction enables scientists to determine the presence of a mutation in the patient’s DNA. Another type of test is using antibodies against a mismatch repair protein (which is not functional in colon cancer cases with microsatellite instability) in order to determine the location of a microsatellite instability. It is crucial to test for microsatellite instabilities because doing so can allow physicians to determine which treatments will best enhance chances of survival.
Testing for microRNA (a short sequence of RNA) expression can also determine the potential presence and amount of microsatellite instabilities. There are specific microRNA sequences that indicate whether the microsatellite instability level is low, medium, or high (Earle, et.al). Looking for specific microRNA sequences could potentially be a more efficient way to look for microsatellite instabilities, since there have been arrays that render little human error. For example, a company called Microculus produces technology-driven arrays that signal whether microRNA is present (“Products”).
There are many other types of short and repetitive sequences of DNA/RNA, such as short tandem repeats, that could potentially be used to evaluate treatment for cancer. It is vital that you take an active role in screening your cancer because chances are, your genome will tell you a lot about the type of treatment that will work best.
Boland, C. Richard, and Ajay Goel. “Microsatellite Instability in Colorectal Cancer.” NCBI. U.S.
National Library of Medicine, 11 Feb. 2011. Web. 04 July 2017.
Buckowitz, A., H-P Knaebel, A. Benner, H. Bläker, J. Gebert, P. Kienle, M. Von Knebel
Doeberitz, and M. Kloor. “Microsatellite Instability in Colorectal Cancer Is Associated with Local Lymphocyte Infiltration and Low Frequency of Distant Metastases.” British Journal of Cancer. Nature Publishing Group, 09 May 2005. Web. 04 July 2017.
Buecher, Bruno, Wulfran Cacheux, Etienne Rouleau, Barbara Dieumegard, Emmanuel Mitry,
and Astrid Lievre. “Role of Microsatellite Instability in the Management of Colorectal Cancers.” Digestive and Liver Diseases. Dld Journal, June 2013. Web. 3 July 2017.
“Colorectal Cancer: Treatment Options.” Cancer.Net. American Society of Clinical Oncology, 16
Feb. 2017. Web. 04 July 2017.
Earle, Jonathan S.L., Rajyalakshmi Luthra, Angela Romans, Ronald Abraham, Joe Ensor, Hui
Yao, and Stanley R. Hamilton. “Association of MicroRNA Expression with Microsatellite Instability Status in Colorectal Adenocarcinoma.” NCBI. US National Library of Medicine, July 2010. Web. 23 July 2017.
Kloor, M., L. Staffa, A. Ahadova, and M. Von. “Clinical Significance of Microsatellite Instability
in Colorectal Cancer.” NCBI. U.S. National Library of Medicine, Jan. 2014. Web. 04 July 2017.
Pino, M. S., and D. C. Chung. “Microsatellite Instability in the Management of Colorectal
Cancer.” NCBI. U.S. National Library of Medicine, June 2011. Web. 04 July 2017.
“Products.” Miroculus. Microculus, 2016. Web. 23 July 2017