Evaluation of Molecular Biomarker Test for Colon Cancer

This essay examines the critical role of molecular biomarker tests performed in the histopathology laboratory for colon cancer diagnosis and treatment selection. The essay focuses on the principles of these tests, including the epidermal growth factor receptor (EGFR), mismatch repair deficiency (dMMR), BRAF, PIK3CA, and PTEN. It details how these biomarkers are used to predict responses to specific treatments, such as anti-EGFR monoclonal antibodies and immunotherapy, and how they guide treatment decisions based on gene mutations within the pathways. The essay also highlights the importance of accurate genomic-based drugs and the increasing role of molecular diagnostic tools in enabling effective treatments for colon cancer patients. The role of histopathology laboratories and the impact of timely stages are also addressed.

Running head: TEST FOR COLON CANCER 1
Molecular Biomarker
Student’s Name
Professor’s Name
Institution Affiliation
Date

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Introduction
Standard Molecular Biomarker is a test that is carried out in the histopathology laboratory
during the process of diagnosing for colon cancer. The standard molecular biomarker is useful in
determining the treatment of colon cancer. It gives guidelines for conventional chemotherapy
methods and identifies the effective therapies for the treatment of colon cancer (Sepulveda et al,
2017).
Principles of Standard Molecular Biomarker
The epidermal growth factor receptor (EGFR). Due to the increased understanding of the
colon cancer pathways, it has resulted to the increase of monoclonal antibodies to the EGFR,
panitumumab so that to block EGFR, thus preventing the activation of the transduction pathway
signals that uses p13-AKT, SRC and RAS enzymatic reactions with ligands like EGFR
Mismatch repair deficiency (dMMR). It causes several somatic mutations to produce neo-
antigens. The dMMR tumors can respond to the blockage of immune checkpoints such as PD1,
PD-LI, LAG-3, and IDO because of the presence of neo-antigens. (Morelli et al, 2015).
BRAF. Oncogene that is present in the RAS-RAF-MAPK pathway which has adversative
prognosis in all the treatments.
PIK3CA. It is a proto-oncogene which encodes for the PI3K involved in the EGFR
tyrosine domain. In recent studies have shown that the mutations of the exon 20 of this proto-
oncogene can act as a target for anti- EGFR therapy resistance. This domain leads to activation
of AKT- mTOR pathway after phosphorylation of AKT.

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PTEN. It is a tumor – suppressor gene which encodes a protein used in suppressing the PI3-
AKT signal path. It lacks consensus and acts as a predictive marker of anti-EGFR treatment
(Punt, Koopman & Vermeulen, 2017)
.
How Molecular Biomarkers are used in Colon Cancer Treatment
The molecular markers predict responses to a particular treatment or therapy that is called
the predictive biomarkers. Treatment of monoclonal antibody marks the epidermal growth factor
receptor and bind EGFR extracellular zone, thus, leading to the blockage of the signal pathways
of EGFR. For colon cancer (colorectal cancer,) patients, Anti- EGFR has been the main target
used for colorectal cancer (CRC) therapies. CRC therapies require the knowledge of genes
mutational within the pathways as the predictive biomarkers of responses towards CRC
treatments.
The CRC patients who have the KRAS triggering mutations which affect exon 2codons
12 and 13 were demonstrated through clinical trials but did not show any effects from anti-
EGFR monoclonal antibody treatments. Other guidelines demonstrating the molecular bio-
testing of EGFR signaling pathways in gene mutations that can affect the CRC responses
towards anti- EGFR antibody treatments involves exons of NRAS, BRAF, PIK3CA and PTEN
The DNA mismatch repair (MMR) status of colorectal cancer might show predictive values in
specific clinical environments. When testing for the CRC patients, MMR is recommendable in
all patients so that to perform a workup testing for the evaluation of any possible Lynch
syndrome. For the patients with immunotherapy, the molecular biomarker demonstrated that it is

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crucial to use microsatellite instability (MSI) testing, which is a marker of deficient MMR
(Topalian, Taube, Anders & Pardoll, 2016).
.
During CRC development and progression, there are alterations of several clinical genes
that include BRAF and dMMR, which have been measured using several metrics of tumor
survival or progress and shown to affect the colon cancer prognosis. The stress on accuracy
genomic-based drugs and post-genomic period provides and a large quantity of new information
and promising data of the new molecular cancer biomarkers, which might become a successful
molecular diagnostic tool. The tool would be efficiently useful in enabling effective treatments of
patients with colon cancer (Bronte et al, 2015).
Many of the histopathological laboratories have been known to delay the treatments of cancer
patients where the molecular biomarkers involve several timely stages. These stages include;
selection of assays, selection of the specimen to be tested, tests ordering, and the turnaround time
while waiting for the results. In recent days, the plethora in the technical approach is effectively
used if the test sensitivity and specificity meets the clinical requirements. The current method
uses several molecular markers in gene panels like next-generation sequencing (NGS) cancer
panels that can assay hundreds of amplicons and genes and with known mutational status in CRC
(Kocarnik, Shiovitz & Phipps, 2015).
Conclusion
It is clearly shown that there several biomarkers and specific exons with accurate
prognostic value in the treatment of colon cancer. The CRC guidelines for selecting test for
cancer require well–established methods for determining and regular developmental updates in

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the management of clinical molecular testing. The molecular biomarker test that involves EGFR
signal pathways provides efficient and effective clinical actionable as negative predictors of
importance to the anti- EGFR monoclonal antibody in the treatments of colorectal cancer.

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Reference
Bronte, G., Silvestris, N., Castiglia, M., Galvano, A., Passiglia, F., Sortino, G., ... & Fanale, D.
(2015). New findings on primary and acquired resistance to anti-EGFR therapy in
metastatic colorectal cancer: do all roads lead to RAS?. Oncotarget, 6(28), 24780.
Kocarnik, J. M., Shiovitz, S., & Phipps, A. I. (2015). Molecular phenotypes of colorectal cancer
and potential clinical applications. Gastroenterology report, 3(4), 269-276.
Morelli, M. P., Overman, M. J., Dasari, A., Kazmi, S. M. A., Mazard, T., Vilar, E., ... & Morris,
J. (2015). Characterizing the patterns of clonal selection in circulating tumor DNA from
patients with colorectal cancer refractory to anti-EGFR treatment. Annals of Oncology,
26(4), 731-736.
Punt, C. J., Koopman, M., & Vermeulen, L. (2017). From tumour heterogeneity to advances in
precision treatment of colorectal cancer. Nature reviews Clinical oncology, 14(4), 235.
Sepulveda, A. R., Hamilton, S. R., Allegra, C. J., Grody, W., Cushman-Vokoun, A. M.,
Funkhouser, W. K., ... & Monzon, F. A. (2017). Molecular biomarkers for the evaluation
of colorectal cancer: guideline from the American Society for Clinical Pathology, College
of American Pathologists, Association for Molecular Pathology, and American Society of
Clinical Oncology. American journal of clinical pathology, 147(3), 221-260.
Topalian, S. L., Taube, J. M., Anders, R. A., & Pardoll, D. M. (2016). Mechanism-driven
biomarkers to guide immune checkpoint blockade in cancer therapy. Nature Reviews
Cancer, 16(5), 275.