Finding Drugs for Hard to Treat Forms of Leukemia

Two recently identified types of acute lymphoblastic leukemia (ALL) are extremely difficult to treat with existing drugs. Children who have Philadelphia chromosome-like ALL (Ph-like ALL) and early T-cell precursor ALL (ETP ALL) are more likely to face recurrence and less likely to survive long term.

Researchers are trying to figure out why this is and are working to find treatments that will give children with these types of leukemia better outcomes – ones that are more on par with what can be achieved for children with other types of ALL. The overall survival rate for ALL is currently more than 85%. But, for children with Ph-like ALL, the 5-year survival rate is closer to 60%.

David Teachey

David Teachey, M.D., a physician and researcher at The Children's Hospital of Philadelphia, has a lab set up specifically to look for drugs that will work on Ph-like ALL and ETP ALL. Teachey, whose work is supported in part by a 4-year, $597,000 grant from the American Cancer Society, is testing a number of different drugs in mice that have been injected with these types of leukemia cells.

Teachey and his team are attempting to target one cellular pathway in particular – the JAK-STAT signaling pathway – as Teachey has found that many of the leukemia samples he has looked at are “addicted to that pathway.” Teachey thinks that if he can turn off that pathway with drugs, the leukemia cells may die.

“We are testing drugs that turn it off in mice and seeing good results,” says Teachey. Another reason Teachey is prioritizing investigating JAK-STAT is because drugs that target this pathway are already in clinical trials for other cancers – and some are already FDA approved for other cancers. This means he may be able to get these new treatments, if effective, to children sooner.

“We are focused on drugs that we can get in the kids quickly,” says Teachey. “We purposely picked drugs that are already out there and approved as it makes it easier to get into clinical trials.”

Teachey hopes to be able to get new treatments to children with relapsed leukemia within the next one to two years. “There are clinical trials being developed right now that are going through regulatory processes, so if things go well, it could move fairly quickly,” says Teachey.

A challenge is that Teachey has to first test any new targeted drug in isolation, to see how it works. Then, if the drug appears to do well (effective and not toxic), he has to test it again in combination with existing chemotherapy agents. This multi-step process is necessary as the targeted drug won’t be used alone – it has to be part of a treatment regimen, says Teachey.

“We don’t expect any one drug will be a magic bullet.” Currently, over the course of a child’s leukemia therapy, he or she may get as many as 10 different medications. “So for these subtypes of leukemia, we are talking about adding a different medication on top, plus the original medications to improve outcomes,” says Teachey.

Long-Term Goal: Get Away From ‘Sledgehammer’ Approach to Treatment

Teachey refers to the current method for treating many forms of leukemia – which involves numerous types of medications – as a “sledgehammer approach.”

Teachey hopes new targeted therapies, like the ones he is working on, will eventually enable doctors to ease up on the harsher, though often effective regimens, used to treat a wide variety of leukemias, not just the rarer types his work focuses on today. “We hope to decrease toxicities from this sledgehammer approach.”

“We have to take baby steps; first we add a new treatment on top of the old ones, and then we can start to look at taking away some of the conventional stuff.” Teachey hopes that the new targeted therapies he is studying will be effective enough to allow doctors to reduce some of the current “sledgehammer” methods.

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