Dr. Anette Duensing provided an interesting discussion at the 2017 GIST Summit pertaining to the potential therapeutic benefit of drugs in GIST for drugs previously approved for the treatment of other conditions.  What follows is a summary of some of her concepts.

1).  A transcriptional Inhibitor called mithromycinA has shown activity against KIT.  MithromycinA has been shown in mouse models to inhibit the transcription of the KIT gene through disruption of the mRNA production process.  MithramycinA is presently not available; however, mithramycinA analogs are under development.

2). The drug Bortezomib (Velcaid), a proteozome inhibitor, has been approved for the treatment of multiple myeloma.  If applied to GIST cells, KIT expression is impaired due to the loss of transcription ability of the cells. Unfortunately, Bortezomib has been shown to have heavy side effects,.  A clinical trial for a second generation drug which may have lesser side effects has been applied for.

3).  Gleevec was initially designed for the treatment of Chronic Myeloid Leukemia (CML), not for GIST.  Gleevec is a KIT inhibitor as well as an inhibitor of BCR-ABL.  There is evidence that that the inhibition of ABL in GIST could provide protection for KIT.  It is therefore theorized that the development of a KIT kinase inhibitor that spares ABL could be of therapeutic benefit in GIST.

4).  Stem Cell Factor plays a role in GIST.  It appears that the drug Synribo, which has been FDA approved for the treatment of resistant CML, could provide benefit in the treatment of GIST through interference with the mRNA process.

To watch Dr. Anette Duensing’s presentation at the 2017 GIST Summit, Novel Therapeutic Strategies for GIST:  Targeting the Tumor and Treating the Whole Patient, follow this link.