The cell cycle refers to the several stages that a certain cell passes from one cell division to the next. It is composed of two main phases: interphase and mitosis. A greater portion of the cell cycle is the interphase which constitutes 90% of the cell cycle process. This phase prepares the cell for its division. This consists of three major stages termed as G1 (growth 1), the S (synthesis) phase and the G2 (growth 2) phase . Mitosis on the other hand constitutes 10% of the cell cycle and this is subdivided further into several stages such as prophase, metaphase, anaphase, and telophase. Mitosis is the stage where the division actually occurs leading to cytokinesis which is not actually a part of mitosis but a period wherein cell has already separated into two identical daughter cells as a result of the division of the cytoplasm (Unviversity of Leicester, n.d.).
University of Leicister (n.d.) The Cell Cycle, Mitosis and Meiosis. http://www2.le.ac.uk/departments/genetics/vgec/schoolscolleges/topics/cellcycle-mitosis-meiosis
The cell has a regulation mechanism in which when something is not perfect in the cell division process, the cell destroys itself in a process known as apoptosis. There are certain checkpoints in the cell cycle which checks for errors in DNA replications and these are located before the end of the G1 phase and before the end of G2. If there are mutations in the DNA that allows the cell to be stimulated to proceed despite changes in the genetic material, cancer occurs as a result of proliferated growth and division of the cells which is a consequence of the mutation.
University of Leicister (n.d.) The Cell Cycle, Mitosis and Meiosis.
http://www2.le.ac.uk/departments/genetics/vgec/schoolscolleges/topics/cellcycle-mitosis-meiosis
Oncogenes are mutated genes which promote cell growth and proliferation. An example of an oncogene is Her2 which is a receptor tyrosine kinase. Her2 is one of the oncogenes that is associated in the development of chronic myeloid leukemia. One of the cancer drugs used to target the protein in the oncogene Her2 is Imatinib mesylate which inhibits signaling pathway kinases (Rang et al 2003).
While oncogenes promote the development of cancer, the body’s cell regulation mechanism in stopping errors in cell growth and proliferation is assisted by certain genes known as the tumor suppressor genes (American Cancer Society, n.d.) . An example of this is the p53 gene which stops cell replication until the DNA of the cell is repaired. The p53 tumor suppressor gene is involved in more than 60% of cancers and it destroys replications that are harmful by activating apoptosis or cell suicide (Weinberg 1996).
A Closer Look at Cancer Drugs
There are many cancer drugs available today and the mechanism of action is very specific to their type. In general, cancer drugs are categorized into three: Direct DNA-Interactive agents, there are also those types that affect the microtubules, and there are those that act at hormone-like receptors (Braunwald et al. 2001). In addition to the mentioned categories, there are also anti-cancer drugs which are still a subject of ongoing several studies and these are the drugs that target specific proteins involved in the cell cycle by inhibiting protein kinases (Lapenna and Giordano, 2009).
Under the direct DNA-Interactive agents are several other types which includes the alkylators which prevent cell proliferation by covalently reacting with the bases of DNA through cross-linking of the two strands or the appearance of breaks in the DNA (Neal 2005). There are also antimetabolites which inhibit purine and pyrimidine synthesis thus blocking the involved metabolic pathways in DNA synthesis in the cell proliferation process. Moreover, there’s also the antitumor antibiotics that damage the DNA of the cell by undergoing electron transfer reactions (Braunwald et al. 2001).
Drugs that target proteins in the cell cycle include the inhibitors of cyclin-dependent kinases such as the R-roscovitine, the inhibitors of CHK1 and CHK2, aurora kinases inhibitors and the polo-like kinases inhibitors (Lapenna & Giordano 2009). Protein kinases are involved in the cell cycle process which is a key cycle regulator in eukaryotic cells. An example of this is the cycle-dependent kinase 1 (CdK1) which when activated initiates events in the mitotic phase through phosphorylation. These anticancer drugs that target protein kinases assists in halting the cell division process by inhibiting protein kinases such as the Cdk1.
The main advantages of the kinase inhibitors is that unlike the direct DNA-interactive agents which are cytotoxic, they are found to have low toxic levels in various clinical studies (Novak 2004). Moreover, it can be used to inhibit target proteins to fight off against a specific type of cancer since mutations on specific types of protein kinases have been associated to a specific type of cancer such as the mutations of the CdK4 which has been linked to melanoma, glioblastoma and breast cancer and the protein Aurora B which has been connected to the development of colorectal and lung cancers (Lapenna & Giordano 2009). An example of an anticancer drug which target proteins in the cell cycle is the imatinib which has been used in the treatment of chronic myelogenous leukemia (Novak 2004).
While DNA interacting agents for cancer therapy can carry unwanted side effects to a cancer patient, its use can also be highly valued when used in a combination with other therapies which holds true for later-stage tumors. Its use together with other classes of drugs in cancer treatment can also provide a degree of efficacy and effectiveness in cancer therapy (Hurley 2002).
REFERENCES: American Cancer Society (n.d.). Genes and Cancer. (online) Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/002550-pdf.pdf Braunwald, E., Fauci, A., Kasper, D., Hauser, S., Longo, D. And Jameson, J.L. (2001). Harrison’s Principles of Internal Medicine. 15th Edition. New York. McGraw-Hill. pp.225-226 Hurley, L. (2002). DNA and Its Associated Processes as Targets for Cancer Therapy. Macmillian Magazines. Volume 2. (online). Available at: http://faculty.missouri.edu/~gatesk/DNAasaTarget.pdf Lapenna, S. and Giordano, A. (2009). Cell Cycle Kinases as Therapeutic Targets for Cancer. Nature. Volume 8. (online). Available at: http://www.nature.com.libezproxy.open.ac.uk/nrd/journal/v8/n7/full/nrd2907.html Neal, M.J. (2005). Medical Pharmacology at a Glance. Fifth Edition. USA. Blackwell Publishing Ltd. Novak, K. (2004). Conference Report - Protein kinase Inhibitors in Cancer Treatment: Mixing and Matching?. Medscape. (online). Available at: http://www.medscape.com/viewarticle/471462 Rang, H.P., Dale, M.M., Ritter, J.M., and Moore, P.K. (2003). Pharmacology. Fifth Edition. Philadelphia. Elsvier Science Limited.
University of Leicister (n.d.) The Cell Cycle, Mitosis and Meiosis. (online) Available at: http://www2.le.ac.uk/departments/genetics/vgec/schoolscolleges/topics/cellcycle-mitosis-meiosis
Weinberg, R. (1996). How Cancer Arises. Scientific American. (online). Available at: http://www.nature.com.libezproxy.open.ac.uk/scientificamerican/journal/v275/n3/pdf/scientificamerican0996-62.pdf
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