So savvy people, if Hallmark #1 of cancer is “sustained proliferative signaling” and we know some of the ways that cancer cells achieve this, then why don’t we just target that mechanism and flip the switch back to OFF? The answer is we CAN and we DO for some of these switches! For example, imatanib (tradename Gleevec) was developed in the 1990s and was approved for use in 2001 for certain types of cancer that have a grow switch stuck in the ON position because of a mutant rearrangement of DNA in cancer cells (BCR/ABL translocation seen in the picture). This is what we call “targeted therapy” because Gleevec targets a specific pathway that we know is abnormal in the cancer cells but that mutant change shouldn’t be found in normal healthy cells. Hence, the drug “targets” only cancer cells.
Two diseases, chronic myelogenous leukemia (CML) and Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL), have this BCR/ABL translocation which results in the grow switch to be stuck ON. Both diseases have been historically hard to treat and often required a bone marrow transplant. However, since the advent of the class of drugs that includes Gleevec, the outcomes are much more favorable. In fact, some CML patients can be on this type of drug indefinitely and live long and healthy lives. Ph+ ALL still requires intensive chemotherapy but bone marrow transplants can be avoided more often than not AND the survival rate has over doubled from 30% to around 70%! Less toxic drugs and improved survival? Winner winner!
The not so good things? As per usual, the approval for this drug in pediatrics lagged way behind its approval in adults. We didn’t get full approval for this drug for pediatric Ph+ ALL until 2013. Additionally, this type of targeted therapy is extremely expensive with an estimated wholesale cost of $120,000 per year (2016 estimate). Lastly, cancer cells are so stinking sneaky, that they can become resistant to chemotherapy and newer generations of this drug have already been developed to combat this problem. However, all in all, pretty cool stuff right?
#morethanfour #ChildhoodCancer365
original image found here
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