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The Development Of Novel Drugs For Chronic Myeloid Leukemia

1002 words - 5 pages

Biomarkers are becoming increasingly important in cancer treatments due to its contribution to the development of specific drugs. A variety of these signature markers has been discovered, such as the BCR-ABL oncogene in patients with Chronic Myeloid Leukaemia (CML). Although traditional therapies can be used in the treatment of a variety of cancers, it cannot kill the nature of this type. CML treatment requires a strategy by means of the combination of drugs in order to succeed in healing.

Chronic Myeloid Leukaemia is a rare cancer that affects white blood cells [5] and extends to its stem cells. In the bone marrow, where the production of myeloid and lymphoid lineage occurs, white blood cells increase in number, leading to less available space for proliferation and maturation of others cell types. In the light of this, immature cells fall into the bloodstream enhancing the malignancy of this tumor. The major characteristic of CML is the presence of the Philadelphia chromosome (Ph) in approximately 95% of all CML cases [6]. This chromosomal aberration is consequence of a somatic mutation and results of a translocation at chromosomes 9 and 22, respectively at the ABL gene and at breakpoint cluster region (BCR) [7], followed by a fusion between them, forming the oncogene called as BCR-ABL [8] [9]. Because Bcr-Abl is present in the majority of the CML population, it has been considered a key feature and a target for therapies.

The definition of biomarkers is extensive, but it encompasses the biological properties which can indicate whether the body is properly functioning or not. Some experts state that they can be natural molecules produced by the body [1], others though consider them biological processes [3] that can be measured and hence a higher understanding of a disease [10]. However, there are still a certain group that says biomarkers can also be imaging scans [10]. They play a role in the discovery of causes, diagnosis, prediction and treatments [4], and also monitor the body’s responses to drugs during a treatment. Bcr-Abl oncoprotein is a well-known molecular marker with a constitutively activated tyrosine kinase domain. In addition, it has two loops stabilized that are targets of mutations, the ATP-binding loop and the activation loop [15]. This protein reaches a wide range of pathways and transcription factors, Ras, PI3 kinase-Akt/PKB, Jak-STAT, and Myc, Jun, Nf-κβ respectively, with the aim of activating many proliferation and survival circuits [6]. Owing to Bcr-Abl properties, it became a desirable target for drugs. Studies confirmed the major influence of the tyrosine-kinase activity of Bcr-Abl on leukemogenesis, and this brought about the development of new drugs, like Gleevec.

The treatment for CML requires combined therapies. Chemotherapy is a traditional method used in many cancers. Nevertheless, in CML it is not sufficient. Depending on the doses taken by the patient, it might have a stronger effect [12]. This would be...

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