Locking leukemia's cellular escape hatch (Selinexor and an AKT inhibitor)

Medical Xpress / Duke University / Nature Cancer ^ | June 8, 2022 | Alissa Kocer / Kevin H. Lin et al

[ConservativeMind]

Leukemia starts in cells that would normally develop into different types of blood cells. Depending on the type of leukemia and the age of the patient, five-year survival rates vary between about 20–80%.

A new class of drugs called nuclear exportin inhibitors has recently been approved for use to treat cancers. Nuclear exportins are proteins that shuttle other proteins out of the nucleus of a cell. These new drugs stop the shuttle from leaving the station.

"The idea is that if you treat cells with a drug that blocks a nuclear exportin," Wood said, "its client proteins become trapped in the nucleus."

The PI3 kinase (PI3K) signaling pathway regulates cell survival and proliferation and is implicated in various forms of cancer. When they knocked out the genes that turn on the PI3K pathway, the drug worked much better. Conversely, when they knocked out the genes that turn off the PI3K pathway, the drug worked much worse.

After that discovery, they took cells and, again, treated them with Selinexor to see if the PI3K pathway was active. "We found something really remarkable," Wood said. "Within hours of the drug treatment, nearly all leukemia cells had profoundly activated the PI3K pathway." In other words, the PI3K pathway turned on because of the drugs. "Without the shuttle to move proteins out of the nucleus," Wood said, "the leukemia cells need an escape route, so they won't die. The PI3K pathway serves this function."

So what happens if you lock the escape hatch?

A class of drugs called AKT inhibitors does just that, and in mouse models, Wood and team found that a combination of Selinexor and an AKT inhibitor work much better than chemotherapy, which is the current standard of care for otherwise healthy patients.

[ConservativeMind]

The write up describes these two drugs (Selinexor and various AKT inhibitors, like Miltefosine) are also in pill form.

[ConservativeMind]

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[libh8er]

For a moment I thought this could be a promising alternative to chemo or transplant until I got to the last line

“ If this treatment can get more people to transplant stage, doctors will be able to save many more lives.”

It’s still the transplant they will potentially save a life. A transplant will require chemo as part of the transplant process, so chemo hasn’t been avoided with this therapy.

[ConservativeMind]

This is too new to prove it cures leukemia. It doesn’t necessarily mean it can’t do so.

It does help, potentially a lot.