Role of the Histopathology Laboratory in Predicting the Response of Patients Tumours to Therapies - Essay Example

?Cellular pathology: Discuss the role of the histopathology laboratory in predicting the response of patients’ tumours to therapies blocking the action of growth factor receptors Introduction Cancerous cells are complex and may affect a patient’s reaction to treatment. Traditional chemotherapeutic sessions were nonspecific and would be administered to patients regardless of their molecular history. This caused unnecessary harm and led to remission of the disease. However, advancements in histopathology have led to a practice known as molecular profiling. This is a paradigm shift in the treatment of cancer as it eliminates side effects and targets only the relevant biological processes. Doctors can determine a person’s treatment plan using one’s molecular characteristics. Once the growth factor pathway of a cancerous cell is determined, practitioners may customize therapy to block those pathways. How histopathology identifies patients suitable for therapy In order to understand the association between histopathology advancements and suitability for therapy, it is necessary to examine different types of cancer and the relationship to their pathways separately. Gastric cancer has various pathways that can be detected and used for molecular therapy. One such route is the MAPK-ERK pathway, which is dependent on the human epidermal growth factor receptor two or HER2. MAPK and ERK bring about the phosphorylation of other proteins during the transfer of information between cell DNA and surface receptors (HER2 is one example). These proteins cause the DNA to propagate cell growth by starting cell division. In patients with gastric cancer, and other cancers as well, a malfunction in this pathway leads to malignancy. Studies show that the presence of HER2 intensifies phosphorylation in these patients (Wong and Yau, 2013). It is possible to detect an over expression of this receptor using molecular techniques. One must conduct a test through microarray analysis. Here, the biological material containing the cancerous cell is placed on a glass slide and analysed through the use of screening methods. If a patient tests positive for this receptor, then they can be eligible for trastuzumab as a treatment option. Analysts have shown that these individuals will respond positively to therapy because of its ability to modify the ERK-MAPK pathway. Trastuzumab blocks HER2’s action in the chain and thus no information is relayed to the DNA of the cancerous cell. This means it will not grow or its rate of growth will be minimised. A diagrammatic illustration of gastric cancer pathways (Wong and Yau, 2013) Lung cancer also has a signalling pathway that can be targeted during treatment known as the PI3K –MTOR pathway. The growth route leads to promotion or inhibition of protein in the cell. The chain starts with PI3K then moves to AKT and finally ends with mTOR. If the pathway becomes deficient, too much protein synthesis will occur that will manifest as lung cancer. EGFR or Epidermal growth factor receptor is a part of the heterodimer kinase group. This receptor plays a significant role in the PI3K-mTOR chain because it activates PI3K, which eventually alters the rate of cell proliferation. If a mutation is present in the EGFR gene, then cell signalling for the above-mentioned chain will not work. Advances in the laboratory have made molecular analysis a central part of lung cancer therapies. Sanger sequencing is a reliable test that may be used to detect these defections in the cell (Pao & Ladanyi, 2007). The molecular biologist must extract DNA from the subject. Thereafter, the DNA product must undergo PCR amplification. Sequencing and interpretation ought to follow this process. Care should be taken to ascertain that at least a quarter of the sample consists of mutant DNA. Since the latter parameter may not be guaranteed, a molecular analyst may choose pleural effusions as an alternative to this method (Ellison et. al., 2013). Treatment options for persons with EGFR include inhibitors of heterodimer kinases. Such therapies may include one of two well-known medications; that is, erlotinib and gefitinib (Brambilla and Gazdar, 2009). The inhibition of biochemical processes signalled by EGFR is facilitated in these treatment outcomes. A diagrammatic illustration of an EFGR pathway (Ellison et. al., 2013) The MAPK-ERK pathway is also relevant in the treatment of ovarian cancer (Smolle et. al., 2013). One of the proteins that regulates this pathway is BRAF, which is a transduction protein kinase. Activities of BRAF thus contribute to cell division and development as determined by the MAPK pathway. If BRAF mutates in patients, it could lead to excessive cell growth and hence cancer. Studies indicate that type 1 ovarian cancer is likely to exhibit this mutation. A patient with such a disease is likely to possess endometrioid or mucinous cancer. In the nucleus of the patient as well as the cytoplasm, ERK will start to over activate its protein kinases such that they will lead to the development of tumours. In this regard, BRAF is an upstream factor in the pathway while the transcriptions are the downstream ones. One of the tests that can be performed in order to establish the presence of a BRAF mutation is the Primer extension PCR. The analyst needs to have an adequate amount of the sample. Thereafter, one should handle the specimen correctly and process it properly. The procedure will involve use of electrophoresis and shifted termination assay. Samples ought to be placed in an appropriate fixative like paraffin and stored at room temperature prior to testing. The method will either show a negative or positive indication of the mutation. Key treatments for this malfunction include dabrafenib and vemurafenib. These drugs will block the over activated MAPK-EPK pathway by inhibiting BRAF activities (Nikiforovf, 2011). It should be noted that even though three types of cancers have been mentioned above, several other types of cancer may also rely on similar tests and similar pathways to determine patient eligibility for cancer treatment. One such case is EGFR in the MAPK-EPK pathway of colorectal cancer. Similar signalling functions are exaggerated in this form of cancer and treatment thus targets the EGFR protein (Efferth, 2012). Likewise, patients with breast cancer will respond positively to therapy if laboratory analysis indicates that they possess the oestrogen receptor. This can be tested through the use of immunohistocehmistry and Tamoxifen offered (Ciocca & Elledge, 2000). Conclusion Signalling pathways that either lead to the inhibition or growth of cells are both affected by genetic mutations. Laboratory histopathology aims at identifying the molecular markers which alter these results. When identified and used, patients will be more responsive to treatment. References Brambilla, E. & Gazdar, A., 2009. Pathogenesis of lung cancer signalling pathways: roadmap for therapies. Eur. Respir. Journ. 33(6 ), pp.1485-1497 Ciocca, D. & Elledge, R., 2000. Molecular markers for predicting response to tamoxifen breast cancer patients. Endorcine 13(1), pp.1-10. Efferth, T., 2012. Signal transduction pathways of the epidermal growth factor receptor in colorectal cancer and their inhibition by small molecules. Curr. Med. Chem. 19(33), pp.5735-44. Ellison, G., Zhu, G., Moulis, A., Dearden, S., Speake, G. & McCormack, R., 2013. EGFR mutation testing in lung cancer: A review of available methods and their use for analysis of tumour tissue and cytology samples. Clin. Pathol. Journal 66(2), pp.79-89. Nikiforovf , Y., 2011. Molecular analysis of thyroid tumors. Mod Pathol. 2, pp.34-43. Pao, W. & Ladanyi, M., 2007. Epidermal growth factor receptor mutation testing in lung cancer: Searching for the ideal method. Clin. Cancer Res. 13, pp.4954. Smolle, E., Taucher, V., Pichler, M., Petru, E., Sigurd, L. And Haybaeck, J., 2013. Targeting Signalling Pathways in Epithelial Ovarian Cancer. International Journal of Molecular Science 14, pp.9536-9555. Wong, H. & Yau, T., 2013. Molecular targeted therapies in advanced gastric cancer: does tumor histology matter? Therap. Adv. Gastroenterol. 6(1), pp.15–31. Read More