If you’ve recently been diagnosed with metastatic melanoma or metastatic colorectal cancer, chances are you’ve had to familiarize yourself with a lot of new terms and complicated concepts. One term you may not have heard before is “biomarker.” As researchers learn more about how cancer cells develop, grow, and spread, more attention is being paid to the role biomarkers play in these processes. For patients, undergoing biomarker testing helps their doctor/healthcare team determine whether or not their cancer was potentially caused by a specific gene mutation.

What is a Biomarker?

A biomarker is a biological, chemical, or biophysical entity that is present in tumor tissues or body fluids.¹

It can be used to:

• Provide information on whether a disease or condition is present
• Provide information about the characteristics of a disease or condition
• Potentially provide some insight into what prescription treatment options may be appropriate for the specific type of cancer.

Mutations in Metastatic Melanoma and Metastatic Colorectal Cancer (CRC)

• There are many types of cancer biomarkers, including genetic mutations that can affect how cancer cells grow, multiply and die. In melanoma and CRC, some mutations include KRAS, NRAS, and BRAF. These mutations are typically seen in patients with metastatic disease or cancer that has spread to other parts of the body.^2,3
• The frequency of these mutations varies widely.
  • KRAS is the most frequently altered gene across all cancer types, with approximately 30%-40% of CRC cases carrying a KRAS mutation.⁴
  • NRAS is the second most common oncogenic driver in melanoma and is altered in 15%-20% of melanoma patients.⁵
  • The BRAF mutation is estimated to occur in approximately 50% of people with metastatic melanoma and approximately 10% of people with metastatic CRC. ^{6, 7, 8, 9, 10, 11, 12, 13, 14}
• Like in most cancers, mutations in melanoma and CRC may increase the growth and spread of cancer cells and can inform prognosis.

What is Biomarker Testing and Why is it Important?

Thanks to ongoing scientific research, doctors now know that certain cancers may be the result of mutations, or changes, that occur in certain genes, which can affect the instructions for cells to grow and divide. Biomarkers can be identified through the process of biomarker testing: a series of tests that evaluate whether cancer-causing mutations may exist.

Biomarker testing helps identify treatment options that may be appropriate for a particular patient, given his or her gene mutation and type of cancer, and may also provide an indication of the presence of an aggressive disease or prognosis.

¹Biomarker analysis for oncology. Future Medicines. Available at: https://www.futuremedicine.com/doi/full/10.2217/bmm.15.60. Accessed October 2020.
²Vacante, M., Borzi, A., Basile, F., et al. (2018). Biomarkers in colorectal cancer: Current clinical utility and future perspectives. World Journal of Clinical Cases, 6(15), 869-881. doi: 10.12998/wjcc.v6.i15.869
³Cicenas, J., Tamosaitis, L., Kvederaviciute, K., et al. (2017). KRAS, NRAS, and BRAF mutations in colorectal cancer and melanoma. Medical Oncology, 34(2), 26, doi: 10.1007/s12032-016-0879-9
⁴Dinu, D., Dobre, M., Panaitescu, E., et al. (2014). Prognostic significance of KRAS gene mutations in colorectal cancer – preliminary study. Journal of Medicine and Life, 7(4), 581-587.
⁵Johnson, D. B., Puzanov, I. (2015). Treatment of NRAS-Mutant Melanoma. Current Treatment Options in Oncology, 16(4), 15. doi: 10.1007/s11864-015-0330-z
⁶Saridaki, Z., Tzardi, M., Sfakianaki, M., et al. (2013). BRAFV600E Mutation Analysis in Patients with Metastatic Colorectal Cancer (mCRC) in Daily Clinical Practice: Correlations with Clinical Characteristics, and Its Impact on Patients’ Outcome. PLoS ONE, 8(12). doi:10.1371/journal.pone.0084604.
⁷Loupakis, F., Ruzzo, A., Cremolini, C., et al. (2009). British Journal Of Cancer, 101(4), 715–721. doi:10.1038/sj.bjc.6605177.
⁸Corcoran, R. B., Ebi, H., Turke, A. B., Coffee, et al. (2012). Cancer Discovery, 2(3), 227–235. doi:10.1158/2159-8290.CD-11-0341.
⁹Sorbye, H., Dragomir, A., Sundström, M., et al. (2015). High BRAF Mutation Frequency and Marked Survival Differences in Subgroups According to KRAS/BRAF Mutation Status and Tumor Tissue Availability in a Prospective Population-Based Metastatic Colorectal Cancer Cohort. PloS ONE, 10(6), e0131046. doi:10.1371/journal.pone.0131046.
¹⁰Safaee Ardekani, G., Jafarnejad, S. M., Tan, L., et al. (2012). The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PloS ONE, 7(10), e47054. doi:10.1371/journal.pone.0047054.
¹¹Vecchione, L., Gambino, V., Raaijmakers, J., et al. (2016). A Vulnerability of a Subset of Colon Cancers with Potential Clinical Utility. Cell,165(2), 317-330. doi:10.1016/j.cell.2016.02.059.
¹²CRC in Focus. Clinical Advances in Hematology & Oncology Volume 16, Issue 5 May 2018. Available at: https://www.hematologyandoncology.net/files/2018/06/ho0518CRC-1.pdf. Accessed April 2020.
¹³Cheng L, Lopez-Beltran A, Massari F, MacLennan GT, Montironi R. Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Mod Pathol. 2018;31(1):24-38.
¹⁴Lieu, CH., Corcoran, RB., Overman, MJ. (2019). Integrating Biomarkers and Targeted Therapy Into Colorectal Cancer Management. Am Soc Clin Oncol Educ Book. 2019 Jan;39:207-215. doi: 10.1200/EDBK_240839. Epub 2019 May 17. PMID: 31099678.