Braf Target

Leukemia is a cancer of blood cells, specifically white blood cells that are responsible for fighting infection. However, the abnormal cells in leukemia do not function in the same way as normal white blood cells. Leukemia cells continue to grow and divide, eventually crowding out normal blood cells. The end result is that it becomes difficult for the body to fight infections, control bleeding and transport oxygen (Medicine Net, 2015). It is estimated that each year, approximately 30,800 individuals will be diagnosed with leukemia in the United

Angiogenesis must be present for this occur, allowing cancer to spread to the blood, "thus the higher the density of new blood vessels within some tumors, the higher is the risk of metastasis of that tumor" (Mandal, 2014). Tumors have been documented to grow and spread without a direct blood supply and due to this physicians' are trying to discover ways to block tumor angiogenesis by investigating natural and synthetic inhibitors called "antiangiogenic agents" (National Cancer Institute, 2011). The goal is to slow the growth of cancer or prevent the disease entirely. According to the National Cancer Institute, "when vascular endothelial growth factor (VEGF) and other endothelial growth factors bind to their receptors on endothelial cells, signals within these cells are initiated that promote the growth and survival of new blood vessels" (2011, p. 1).

Oncogenes were discovered in the 1960s, when it was discovered that some animal cancers such as lymphomas were caused by viruses. Some of these viruses were notable due to the simplicity of their RNA genome. These viruses only had three distinct transcription units, involved in the replication of the virus (coat proteins and reverse transcriptase etc.), and an extra gene. This was an oncogene. When oncogenes are properly functioning they are termed proto-oncogenes (Todd R, 1999). Their normal function is to control cell proliferation. These function in growth signalling pathways, and conversely to tumour suppressing cells are activated through a gain in function rather than a loss of it. This occurs in two ways, by producing more of a product, or producing a subtly different product, as a result of a mutation similar to tumour suppressor genes (Croce, 2008). Oncogenes play a particularly strong role in the development of breast cancers. Often the normal ERBB2 and other related genes are amplified in late stage neuroblastomas and rhabdomyosarcomas. ERBB2 encodes HER2 which is a member of the epidermal growth factor

BRCA1 and BRCA2 are tumor suppression genes known as caretakers that are responsible for maintaining the cell genome during cell

PI3Kδ plays an essential role in B-cell receptor (BCR) signaling. PI3Kδ is expressed in lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) [1].

Melanoma is a skin cancer derived from melanocytes and is considered to be the most common fatal malignancy of young adults. About 60% of melanomas harbor a mutation in BRAF, a serine/threonine protein kinase involved in promoting MAPK signaling and cellular proliferation. Of these, 90% harbor the BRAFV600E mutation. To combat this disease, the BRAF inhibitor, vemurafenib, was approved in 2011 to treat late-stage melanomas that are driven by the BRAFV600E mutation. Despite the immediate, positive clinical response to the drug, resistance develops after 7 months of vemurafenib treatment. Significant research effort has been devoted to understanding the origin of this drug resistance, but few studies have examined the fate of individual cells

• Targeted therapy. This treatment targets specific parts of cancer cells and the area around them to block the growth and spread of the

It is worth pointing out that Tafinlar (Debrafenib) only works for melanomar skin cancer where a change in the BRAF gene/protein has been observed. The BRAF gene is responsible for cell growth and division; therefore if unwanted changes happen in this gene, melanomar skin cancer is inevitable. What Tafinlar (Debrafenib) effectively does is to stop further production

Chronic myelocytic (or myelogenous) leukemia (CML) is a rare disease worldwide 2000); however, the innovative advances and successes of CML’s targeted-molecular therapy have kept CML “at the forefront of scientific attention” (Lee 2000). Like other forms of leukemia, CML is a type of cancer that starts in the blood-forming cells of the bone marrow. In particular, CML begins in myeloid stem cells, the cells that differentiate into platelets, red blood cells, and some white blood cells (e.g., granular leukocytes). These cells undergo genetic changes that cause white blood cells to not function normally and divide rapidly. The resulting abnormal leukemia cells build up in the bone marrow and interfere with the production of normal blood cells (platelets, RBCs, and granular leukocytes). Additionally, leukemia cells move into the blood stream and can spread to other organs (e.g., spleen). Unlike acute leukemia, which progresses very quickly, chronic leukemia progresses more slowly and can take a long time before causing health problems (American Cancer Society). According to the American Cancer Society, “one person in 55 will get CML in their lifetime in the United States” (American Cancer Society). The occurrence of the disease increases with age (average age of CML diagnosis: 64 years) and is rarely seen in children. For an unknown reason, slightly more males have CML as compared to females. The one potentially controllable risk factor is exposure to

Adaptive immunity develops after exposure to agents such as microbes, toxins or other foreign substances. Adaptive response is a highly specific response that relies on two types of lymphocytes; T cells that mature in thymus and B cells that mature in the bone marrow. The B-cell receptor or BCR is a transmembrane receptor protein located on the outer surface of B cells. The receptor's binding moiety is

1) The Philadelphia chromosome is chromosome 22, which has undergone a reciprocal translocation with chromosome 9, such that the long arm of chromosome 22 has been replaced with the long arm of chromosome 9. This chromosome is relevant to cancer because the long arm of chromosome 9 contains human c-abl oncogene, which becomes fused to the breakpoint cluster region (bcr) in the Philadelphia chromosome, following translocation. Presence of this bcr-abl gene fusion produces a poorly regulated tyrosine kinase, which results in a much higher level of cell proliferation. The action of this tyrosine kinase results in chronic myelogenous leukemia (CML) symptoms, such as overproduction of white blood cells.

Tumor suppressor gene tells the when to die, repair the mistakes made in the DNA, and slow down cell division. If a tumor suppressor gene gets mutated the cells will grow out of control with nothing to stop them. The mutation can be caused when this gene isn’t activated. Two common example of a tumor suppressor are the p53 and NF1. Proto oncogenes codes for protein which helps with the cell cycle, prevents differentiation in cell, and programs cell death. If a proto oncogenes gets mutated there would be change in the protein sequence which would interfere normal cell regulations. The name of the proto oncogene was oncogene. DNA repair identifies incorrections and damages and fixes them. These three genes are mostly used to find cancer because

Additionally, various forms of Cellular Stress activates another pathway such as Gamma- and UV radiation. It occurs by altering the permeability of the mitochondria which in turn releases Cytochrome C (CytoC) and forming the Apoptosome- a catalytic multiprotein platform that activates Caspase 9. Active Caspase 9 cleaves Caspase 3 which results in downstream events involved in cell death. The release of CytoC is regulated by the Bcl2 family proteins. Bcl2L (Bcl2-Like), BclXL (Bcl2 Related Protein Long Isoform) and other Anti-Apoptotic Bcl2 family members exist in in the outer mitochondrial membrane and prevent CytoC release. BAX (Bcl2 Associated X-protein), BID (BH3 Interacting Death Domain) and BIM (Bcl2-Interacting Protein) are originally inactive and must translocate to the mitochondria in order to induce Apoptosis, either by the formation of pores in the mitochondria directly or by binding via BH3 domains to Bcl2, BclXL and Bfl1, and antagonising these Anti-Apoptotic proteins.

This includes covalent modifications of the p53 gene (altering positive and negative feedback loops in the signaling pathway). P53 gene can be modified at twenty sites, which can change the protein’s behavior in a number of ways. Phosphorylation can inhibit or stimulate protein activity. The attachment or removal of modifying groups controls the behavior of a protein changing it’s activity or stability, which could permit the production of large quantities of the desired protein. Through posttranslational modifications of the p53 gene, this could mediate the control of P53 gene expression through the wnt signaling pathway. The p53 circuit communicates with the Wnt-beta-catenin, IGF-1-AKT, Rb-E2F, p38 MAP kinase, cyclin-cdk, p14/19 ARF pathways. Wnt proteins bind to receptors on the surface of a cell, switching on an intracellular signaling pathway that ultimately leads to the activation of a set of genes that influence cell growth. Wnt transmits its signal by promoting accumulation of free beta-catenin proteins which migrate from the cytoplasm to the nucleus to bind to TCF transcription regulators, creating a complex that activates the transcription of various Wnt-responsive genes, including genes whose products stimulate cell

The inability of the functionality of these genes disrupts apoptosis, programmed cell death and DNA repair which results in cancer, the regulation and dividing of cells out of