The signaling pathways are considered closing which is caused by the binding and stabilization however the signaling pathways had a role in helping leukemogenesis. BRC/ABL becomes a constitutively active tyrosine kinase; this allows imatinib to decrease the activity in BRC/ABL. The ABL protein found in benign cells are inhibited by imatinib. However, the cells can continue to function due to the presence of redundant tyrosine kinases. Many cancerous cells have a large reliance on BCR/ABL. The cancerous cells die due to the lack of performance of the...
The signaling pathways are considered closing which is caused by the binding and stabilization however the signaling pathways had a role in helping leukemogenesis. BRC/ABL becomes a constitutively active tyrosine kinase; this allows imatinib to decrease the activity in BRC/ABL. The ABL protein found in benign cells are inhibited by imatinib. However, the cells can continue to function due to the presence of redundant tyrosine kinases. Many cancerous cells have a large reliance on BCR/ABL. The cancerous cells die due to the lack of performance of the anti-apoptotic functions; this occurs when tyrosine kinases inhibit and stimulates the entry into the nucleus.
Ponatinib is one of the most recently discovered drug to help patients who have grown a resistance to the common drugs used such as Dasatinib. Ponatinib is a multi-target kinase inhibitor, BCR/ABL tyrosine kinase protein is the drugs primary target as the protein develops chronic myeloid leukemia and is constitutively active. The BCR and ABL gene are known as the Philadelphia chromosome which the protein grows from the binding. Ponatinib is effective for patients who are resistant to alternative drugs for treatment. However, ponatinib is very effective because both tyrosine kinase activity in ABL and T315I mutant kinases are inhibited by ponatinib. The structural resistance in the T315I mutation in cells avoids BCR/ABL inhibitors and ABL kinase to bind. Ponatinib doesn’t only have a primary target (BCR/ABL), it also targets the isoforms which transport the mutations that allow the treatment of resistance with the present tyrosine kinase inhibitors. Especially the T315I mutation which has no existing therapy that is effective.
