Many years ago alpha-interferon was trumpeted as wonder drug for cancer. I remember the government stumping up £8 million to buy the entire stock of Wellcome's interferon to treat some desperate child dying of cancer. We now know that interferon has very little, if any, place in cancer therapeutics, but in the test tube interferon certainly acts as a tumor suppressor.
Workers in Toronto have demonstrated that in some cases of CLL interferon may be associated with aggressive disease.
Interferons normally suppress tumor growth by phosphorylating and activating STAT1, but also briefly activate STAT3 (STAT stands for signal transducer and activator of transcription). In CLL with poor prognostic features like del 17p and del 11q, the duration of STAT3 activation is prolonged. This activation is associated with an increase in cell size and number. There was also an association with high levels of reactive oxygen species.
Interferons are produced in response to viral illnesses and this phenomenon could account for deterioration in some cases of CLL in association with a viral illness. TYK2 inhibitors or anti-oxidents given with alpha interferon might have a place in the therapy of aggressive CLL.
3 comments:
Terry,
My biochemistry is weak.
Please help me understand:
TYK2 inhibitors or anti-oxidents given with alpha interferon might have a place in the therapy of aggressive CLL.
I thought interferon was bad news in CLL. And how do anit-oxidants or the TYK2 help?
Thanks
Brian
Interferon is an effective treatment for those cases of CLL that don't need treatment, but not for aggressive CLL, perhaps because it causes prolonged activation of STAT3.
STAT3 is phosphorylated by TYK2 so anything that inhibits TYK2 will halt the prolonged activation of STAT3. There is a small molecule, AG9, and the authors have used this in the test tube to demonstrate this effect. They also showed that antioxidants had the same suppressent effect. These agents had no effect on the activation of STAT1 so the idea is that they might make interferon an active drug for all cases of CLL.
"Interferon is an effective treatment for those cases of CLL that don't need treatment"
Rarely do we get to see such a short and eloquent way to make a point!
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