Monday 3 July 2017

IDH1-inhibitor drugs?

Hello all,

I've not fully understood how mIDH1-inhibitors work? I know they reduce 2-HG levels but does that lead to tumour regression, or is there some other mechanism simultaneously?

I've been looking into different mIDH1-inhibitor trials, but have doubts if they work as monotherapy?

Br,
Juha

1 comment:

  1. In leukemia trials, IDH inhibitors are found to cause cell differentiation. The simple definition of cell differentiation is "The normal process by which a less specialized cell develops or matures to possess a more distinct form and function." In cancer therapy, cell differentiation is a good thing.

    http://www.bloodjournal.org/content/early/2017/06/05/blood-2017-04-779447?sso-checked=true
    Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response
    [Enasidenib was previously known as AG-221, and is an inhibitor of mutant IDH2]

    The accumulation of 2-hydroxyglutarate has many different effects, including a blocking of cell differentiation.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465106/

    In fact the very first paper on a small molecule mutant IDH inhibitor for glioma was entitled "An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells"
    https://www.ncbi.nlm.nih.gov/pubmed/23558169

    Differentiation therapy can be very effective for some types of cancer, and is the standard treatment for acute promyelocytic leukemia, which is treated with all trans retinoic acid, a differentiating agent.

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