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Discussion of a paper in the April 2003 issue of Seminars in Hematology
Imatinib Mesylate in Combination with Other Chemotherapeutic Drugs: In Vitro Studies
It shows how researchers are thinking of new drug combos to prevent resistance to imatinib from occurring.
Now an imatinib-resistant CML cell can arise as a result of natural mutation. Imatinib is killing all the normal Ph cells, and in this environment, the resistant clone can proliferate and multiply sufficiently to start showing up in PCR, FISH and even cyto.
So an obvious strategy to prevent this happening is to add some drug to be taken with imatinib, which can kill the resistant clone.
Everytime a clone shows up, the other drug kills it before it becomes a problem. There are 2 approaches:
1. add a standard chemotherapeutic drug to be taken with imatinib. This will kill the clone but the drawback is that it will damage normal cells as well. The advantage is that there are many available, they are well-characterized and already FDA approved
2. add a molecularly-targetted drug designed to kill the clone. The advantage is that it will not kill normal cells. Potential disadvantage is that it may not be available now, and there can be potentially many types of clones
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