Research Paper

Write a 7-9 page (5-7 pages of text + 2-4 pages of figures and references) research paper based on scientific literature using a minimum of 7 primary literature articles and possibly 2-3 review papers for deeper understanding, minimum 10 citations.

Monoclonal Antibodies: Therapeutic use against Colorectal cancer metastasis

Colorectal cancer (CRC) is one of the leading causes of death, taking millions of lives every year, around the world. It is a malignant form of cancer and is highly metastatic. The treatment for this cancer not only involves the treatment of the primary site of tumor formation but also of the tumors at the metastatic site. Targeted cancer therapy using monoclonal antibodies is one of the most promising methods of treatment. The primary colorectal cancer tumors showed Epidermal Growth Factor Receptors. These molecules were used as a target for monoclonal antibodies to attach and destroy the primary tumors. However, the malignant tumors of the same did not show a correlation with EGFR based monoclonal antibody treatment. This is creating a great issue in using monoclonal antibodies against metastatic tumors. Various other markers are expressed on these tumors. These markers can be used as targets for monoclonal antibodies. (Xu. et. al., 2013) For instance, HLA antigens can be used as targets for monoclonal antibodies. (Ruiter. et. al., 1984) Here I will review what other markers can be used for targeted Monoclonal antibody treatment.

1. There are several elements in the field of targeted cancer therapy that needs an introduction.

A type of antibody that binds to a single type of antigen or a part of the antigen referred to as the epitope, is known as a monoclonal antibody. (Waldmann. et. al., 1991)

Monoclonal antibodies are engineered using the hybridoma technology, in which mammals such as mice are exposed to the antigen of interest. Research to make humanized monoclonal antibodies is ongoing. (Penichet. et. al., 2004)

This antigen causes the immune system of the organism to produce antibodies. The B-cells are then harvested and fused with myeloma cells, forming a hybridoma, such that it has the specificity of the B-cells and the longevity and reproducibility of the myeloma cells. (Milstein. et. al., 1999)

Monoclonal antibodies are manufactured in a way that they recognize a specific antigen, that is the target molecule, bind to it, and destroy the cells with the antigen. (Liner. et. al., 1989).

1. Colorectal cancer is one of the most aggressive types of cancer. It is highly metastatic in nature.

The fourth most common cancer in males is Colorectal Cancer. Factors like obesity, inactivity, a diet low in vegetables and fruits, smoking can contribute to this cancer. (Center. et. al., 2009)

Colorectal cancers develop due to mutations in the DNA, which is common for any other cancer. The mutations can occur in tumor-suppressor genes, oncogenes, and genes involved in the DNA repair mechanism. (Fearon. et. al., 1990)

The primary and the metastatic cancer markers differ. EGFR is a common marker in the primary tumor cells. This is used as a target for the monoclonal antibodies. (Scartozzi. et. al., 2004).

1. Markers that are present on malignant tumors and tumors at the metastatic sites are distinguishable from those expressed on the primary tumors.

Anti-epidermal growth factor receptors are highly expressed on metastatic tumors. Monoclonal antibodies can be used to target these markers. (Xu. et. al., 2013)

The expression of HLA antigens on malignant tumors is also high. These targets can be used to design monoclonal antibodies to track metastatic tumors and destroy them. (Ruiter. et. al., 1984).

Colorectal cancer is one of the leading causes of death in males. Various factors give rise to CRC. It is highly malignant and metastatic in nature. Targeted cancer therapy using monoclonal antibodies is one of the most promising methods of treating CRC. Understanding the difference between primary and malignant tumor cells of colorectal cancer is important. The different markers on the malignant cells are distinguishable from the markers expressed on the primary tumors. These markers can be used as a target for monoclonal antibodies to be used for targeted therapy. Research is required to discover new markers, and create humanized monoclonal antibodies such that it does not cause an immunological reaction towards it.

References

Liners, F., Letesson, J. J., Didembourg, C., & Van Cutsem, P. (1989). Monoclonal antibodies against pectin: recognition of a conformation induced by calcium. Plant physiology, 91(4), 1419-1424.

Scartozzi, M., Bearzi, I., Berardi, R., Mandolesi, A., Fabris, G., & Cascinu, S. (2004). Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies. Journal of clinical oncology, 22(23), 4772-4778.

Xu, Q., Xu, A. T., Zhu, M. M., Tong, J. L., Xu, X. T., & Ran, Z. H. (2013). Predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer treated with anti‐epidermal growth factor receptor monoclonal antibodies: A meta‐analysis. Journal of Digestive Diseases, 14(8), 409-416.

Ruiter, D. J., Bergman, W., Welvaart, K., Scheffer, E., van Vloten, W. A., Russo, C., & Ferrone, S. (1984). Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinants of HLA antigens. Cancer research, 44(9), 3930-3935.

Waldmann, T. A. (1991). Monoclonal antibodies in diagnosis and therapy. Science, 252(5013), 1657-1662.

Penichet, M. L., & Morrison, S. L. (2004). Design and engineering human forms of monoclonal antibodies. Drug development research, 61(3), 121-136.

Milstein, C. (1999). The hybridoma revolution: an offshoot of basic research. Bioessays, 21(11), 966-973.

Center, M. M., Jemal, A., Smith, R. A., & Ward, E. (2009). Worldwide variations in colorectal cancer. CA: a cancer journal for clinicians, 59(6), 366-378.

Fearon, E. R., & Vogelstein, B. (1990). A genetic model for colorectal tumorigenesis. cell, 61(5), 759-767.

Jean, G. W., & Shah, S.R. (2012). Epidermal Growth Factor Receptor Monoclonal Antibodies for the Treatment of Metastatic Colorectal Cancer. Journal of the American College of Clinical Pharmacy, 28(6), 742-752.