The progression of cancer is one of the biggest concerns in the world even though there have been advances in the development of technology which aids in the detection of the disease and therapy but unfortunately, there is still a large mortality rate. With the use of biotechnological tools (genomics, proteomics and bioinformatics) we have seen breakthroughs in the discovery of anti-cancer drugs in which aim to make cancer prevention more readily aware to the public, and to reduce mortality rates.
According to Rang (2006), the role of genomics in the development of cancer has enabled researchers to identify new targets for cancer therapy. The study of human cancer genome is the process of identifying the collection of genes and mutations within the cancer prone families and patients. It is looking at not only the development of a cancer cell but its overall progression (uncontrolled metastasizes) as can be seen in the figure 1 below (National Cancer Institute, 2005).
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Figure 1 - Cancer Genomics, National Cancer Institute, 2005
By studying the human cancer genome, cancer cells can be detected by screening for a particular allele which is shown as marker gene and these occurs in patients who are affected by cancer. Overall, the diseased gene can be estimated as well as the novel drug target such as topoisomerase-1.
New anti-cancer drugs are designed based on:
- Metabolic variation study of the genome
- Transcriptome as they assist in the identification of molecular changes in cancer tissues
-locate proteins used for therapeutic drug development (Mount and Pandey 2005).
The processes in the genome analysis are as follows:
- comparative genome hybridization
- single nucleotide polymorphism (SNP) analyses
All these approaches involve the organization of large data sets (Mount and Pandey 2005).
Overall, the use of genomics will assist the drug discovery and drug development teams to determine the drug target for a new anti-cancer drug.
The National Cancer Institute (2005) acknowledges that 'the human proteome is said to be dynamic as it is changing continuously due to the needs of the body, but it is characterised differently in everyone. Not only changes are made according to the body but as well as in response to cancer and other diseases hence, the proteome of an organism is said to be described as far bigger and very specific compared to genome. In proteomics it provides information on the secreted proteins derived from cancer which enters the bloodstream as well as other bodily fluids and based on this discovery researchers are using this to locate patterns of proteins called protein signatures. According to the National cancer institute (2005), This way information they are able to obtain a better knowledge about the risk, presence, and progression of cancer hence overall, design individual patient's treatments'.
According to Yan et al., (2006) proteomics is the study of all the entire protein which based on several factors such as; their identity, biochemical properties, functional roles, and how their quantities, modifications, and structures change during development and in response to internal and external stimuli.
There are several techniques in which proteomics can help in the development of a new anti-cancer drug, but the clear technique which stands out is the identification of secreted proteins which are able to serve as biomarkers of the disease (Yan et al., 2006). The role of these biological markers assists in the following ways: detection, diagnosis, treatment, monitoring, as well as, prognosis of the disease (Reymond, 2007). Splicing of the respective mRNAs and post-translational modifications are examples of tools where these technologies help with the identification of the changes in the proteins caused by the disease process. One clear advantage to this is those biological endpoints are the identified proteins (Reymond, 2007). Here, changes occur to the proteins where we see the transformation of a healthy developed into a neoplastic cell where it consist of any altered expression, differential protein modification and even changes in specific activity can occur (Yan et al., 2006).
There are two approaches are at presently being carried out in cancer proteomics researches which include protein identification and pattern recognition.
For protein identification, researchers can use several different techniques. An example could include being aware of a certain cancer type and antibodies can then be isolated and selected so that they would bind to proteins thought to be over expressed in that cancer type (Yan et al., 2006). They are placed into a protein microarray and a sample of blood or fluid can be washed over. Fluorescence microscopy can then be used to detect the proteins that have been bound to these antibodies and later can be used to compare with patients without the disease.
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In addition, (Rang 2006, p85) suggests that gel-based electrophoresis techniques has the ability to isolate proteins where based proteins based on their mass and electrical charge can be separated. The proteins in cancer patients can be isolated using this method and with the assistance of an enzyme-linked immunosorbent assay (ELISA) these proteins can be identified where this technique is very similar to microarrays (Srinivas 2002). Further, from a particular research gel electrophoresis (2-D DIGE) coupled technqie was carried out to investigate tumor-specific changes in the proteome of human colorectal cancers where over 1500 protein spot-features were analyzed in each paired normal/tumor comparison (Friedman et al., 2003).
The other technique involves the use of mass spectrometry (MS) is used in pattern recognition. Based on this tool the masses and relative amounts of all proteins in a particular biological sample can be measured. The importance of identification of the actual proteins is to create a protein profile which reduces the possibility of differences in the protein profile that it is obtained during the biological samples derived from patients with and without cancer (Srinivas 2002).
In discovering a new cancer drug, the tools outlined above are all important in discovering the nature of the proteins in patients with and without the disease as these individual techniques have been a key role in the discovery of new cancer drugs. As proteomics acknowledges the arrangement of tools for detecting, isolating and characterising proteins in cells and tissues which will continue to provide important information in underlying the characteristics of proteins in that of the cancer patients. In turn, this tool has helped in the approach to identify drug targets in cancer.
Bioinformatics tools and resources are used in storing and handling large amounts of biological data collected over several years of research as well as in terms of in genome-based therapies. It's key role is to bring together information on the entire range of the human genes and proteins (Rang, 2006, p77). Another important role it plays is investigating sequence and molecular data to identify the genetic variations in individual tissues (Mount and Pandey 2005).
When developing a new cancer drug bioinformatics resources can be used to consult multiple databases which covers the cancer genes and their function as well as, the tissues likely to be affected from a cancer gene (Mount and Pandey 2005). This tool enables researchers to compare and distinguish any similarities or even differences in the genetic makeup of any existing cancers to a new type of cancer in order to pursue a potential form of drug discovery.
These tools include the following; a well-organized management, organization of biological as well as, medical information into precise data as well as, being able to incorporated data management so that the process of determining drug targets and drug-gene interactions can be carried out (Mount and Pandey 2005). In order to understand the response of individuals to drugs bioinformatics consist of many functions such as; analyzing target genes, their nucleotide polymorphisms, protein structures, protein-protein interactions, protein modification sites for degradation, activation, and even have the ability to organise the receptors (Mount and Pandey 2005).
Genetic changes occur in diseased cells where their metabolism can be altered (Mount and Pandey 2005). Bioinformatics tools of data analysis can aid in determining these genetic differences as well, developing simple tests for treatments individual patients .
A particular example in which bioinformatics tool which is currently used is called the "Cancer Biomedical Informatics Grid" which allows for such complex data to be shared between various cancer centers engaged in research. In terms of discovering a new anti-cancer drug, bioinformatics data bases can be shared easily among different organizations and biotechnology companies furthermore, to obtain compatibility of a collection of information already researched. Many websites have been developed with databases which address information on human genes and proteins and other organisms.
With the advancement of technologies in genomics and proteomics, this will enable researchers to gain a better knowledge into the molecular complexity of several types of cancer especially, colon and bowel cancer and thus enable the improvement of tools to facilitate in individual treatments as well as in detection and prevention (Mount and Pandey 2005). By incorporating resources and understanding databases, bioinformatics plays a key role in the progress and application of a new anti-cancer drug.
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