Colorectal cancer, also known as bowel cancer, is the second most common cancer diagnosed in both men and women worldwide and is more common in people over the age of 50. Colorectal cancer refers to cancers originating in both the colon and rectum.

For the majority of colorectal cancers, development begins with the formation of polyps (adenomas), which are pre-cancerous growths usually caused by a mutation in the APC gene. ^[1] Approximately 15% of adenomas progress into carcinomas (cancer) within 10 years, triggered by mutations in other genes including RAS gene family and TP53.^[2]

How can genomic testing benefit me?

While ‘colorectal cancer’ refers to all cancers originating in the colon and rectum, not all colorectal cancers are the same. Colorectal cancer is a highly heterogeneous disease, meaning it has diverse genetic and clinical features which can influence your response to treatment. ^[2] Genomic testing can be used to analyse the DNA of your tumour and may identify the genetic mutations that are unique to your cancer. Identifying these mutations is the key to developing personalised treatments.

Clinical trials have shown that personalised therapies, developed from genetic testing of tumours, are the most effective way to improve treatment outcomes. Patients undertaking therapy as a result of genetic testing are shown to have longer progression-free, higher response rates to treatment and overall greater survival rates. ^[3-5] The cost of investing in genomic testing to obtain a complete and accurate diagnosis is small, compared to the time and money that may be wasted on generic or ill-chosen therapies. Genomic testing provides a powerful diagnostic tool, and every patient deserves an accurate diagnosis.

The power of genomic testing in Colorectal Cancer

Depending on the type of testing done, a comprehensive genomic analysis may provide information on potential therapeutics, development of resistance to treatments, prognosis and disease tracking, and may provide access to clinical trials and new treatments. Genomic sequencing of your colorectal cancer may identify:

• TP53mutations, which are associated with higher resistance to some chemotherapy, helping to guide treatment choices. ^[6-8]
• KRASmutations, which may indicate a better response to RAF or MEK inhibitors, when used in conjunction with PI3K/AKT pathway inhibitors or chemotherapy. ^[9,10]
• BRAFmutations which are associated with a lack of response to anti-EGFR therapy, such as cetuximab and panitumumab, helping to guide treatment choices. ^[11]
• Many other mutations in >120 genes* that will help guide your treatment by highlighting potential drug targets or drug resistance and prognosis, as a small percentage of tumors will have rare mutations that may be targetable with specific treatment options.

What testing options are available?

Codex Pro Plus Solid Tumour Analysis

• The Comprehensive PlusSolid Tumour Analysis is a comprehensive cancer panel that may detect DNA mutations and RNA fusions across >120 key genes that are commonly indicated in a range of cancer types.
• Some of the most commonly mutated genes found in colorectal cancers includeTP53, KRAS, BRAF, PIK3CA, ESR 1, FBXW7, SMAD4, and NRAS, all of which are covered by this test.
• Your personalized report will provide you with the genetic characteristics of your tumor, which may provide information on potential therapeutics, resistance to therapeutics, prognosis and clinical trialsor new treatments you may be able to access.

Cell-Free Tumour DNA (ctDNA) Testing and Tracking

• Tumours may release small fragments of DNA (ctDNA) into the bloodstream, which may contain identical mutations to those identified in the primary tumour.
• As ctDNA is released into the bloodstream, this allows for a liquid biopsy to be performed from a blood draw. This may eliminate the need for invasive procedures to obtain samples, such as biopsies, which can be painful for patients or may not be possible due to the size or location of the tumour.
• ctDNA can be tracked over time to monitor your response to treatment and development of resistance to treatment. ctDNA testing can also be used to check for residual cancer following treatment and can reflect tumour size and burden more accurately than other diagnostic techniques.

Ready to take control of your treatment plan?

Codex Genetics Center aims to educate patients and their families on their cancer types and empower them with the knowledge to take control of their treatment plans. As each patient’s case is unique, there is no “one size fits all” when it comes to testing. We encourage you to contact Codex center, and we can work with you and your oncologist/specialist.

References

1. Marmol, I., C. Sanchez-de-Diego, et al. (2017). Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Int J Mol Sci18(1)
2. Jardim, D. L., M. Schwaederle, C. Wei, J. J. Lee, D. S. Hong, A. M. Eggermont, R. L. Schilsky, J. Mendelsohn, V. Lazar and R. Kurzrock (2015). “Impact of a Biomarker-Based Strategy on Oncology Drug Development: A Meta-analysis of Clinical Trials Leading to FDA Approval.” J Natl Cancer Inst 107(11).
3. Schwaederle, M., M. Zhao, J. J. Lee, A. M. Eggermont, R. L. Schilsky, J. Mendelsohn, V. Lazar and R. Kurzrock (2015). “Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials.” J Clin Oncol 33(32): 3817-3825
4. Subbiah, V. and R. Kurzrock (2016). “Universal genomic testing needed to win the war against cancer: Genomics is the diagnosis.” JAMA Oncology 2(6): 719-720
5. Petitjean, A., M. I. Achatz, A. L. Borresen-Dale, P. Hainaut and M. Olivier (2007). “TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes.” Oncogene26(15): 2157-2165.
6. Mogi, A. and H. Kuwano (2011). “TP53 mutations in nonsmall cell lung cancer.” J Biomed Biotechnol2011: 583929.
7. Govindan, R. and J. Weber (2014). “TP53 mutations and lung cancer: not all mutations are created equal.” Clin Cancer Res20(17): 4419-4421.
8. Holt, S. V., A. Logie, et al. (2012). “Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055).” Cancer Res72(7): 1804-1813.
9. Hochster, H. S., W. A. Messersmith, et al. (2013). “Second-line therapy of KRAS-mutated (KRASm) metastatic colorectal cancer (CRC) with the MEK inihibitor selumetinib ([SEL], AZ6244, ARRY-142886) in combination with irinotecan (IRI): An AGICC study.” J Clin Oncol31(suppl 4): abstr 380.
10. De Roock, W., et al. (2010). “Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.” Lancet Oncol11(8): 753-762.