Blood: Targeting GCK Paths . . . A new option for treating RAS mutant MM.

Frequent mutations in NRAS, KRAS, or BRAF have been found in up to 50% of newly diagnosed multiple myeloma (MM) patients.
NRAS, KRAS, and BRAF mutations occur in hot spots, causing the corresponding protein to have a compositional activation.
, RAS mutations in targeted MMs will improve treatment efficiency and have the potential to overcome drug resistance.
researchers have found that GCK is a new therapeutic target for RAS mutant MM.
internal and external experimental results of MM cells that knock out the GCK gene show that silent GCK inhibits the growth of MM cells, blocks phosphorylation of MKK4/7-JNK, and can affect the degradation of IKZF1/3, BCL-6 and c-MYC.
these effects are saved by expressing a shRNA resistance GCK, thus eliminating the potential non-target effects of GCK gene knock-out.
In contrast, GCK kinase death mutants (K45A) that over-express shRNA resistance inhibit the proliferation of MM cells, do not save the GCK gene knock-out inhibition of MM cell growth, and show that GCK kinase activity plays a key role in regulating the proliferation and survival of MM cells.
important, the high sensitivity of RASMut cells to the knockout of the GCK gene suggests that targeting GCK is effective for MMs carrying RAS mutations.
GCK inhibitor TL4-12 can reduce the expression of IKZF1 and BCL-6, inhibit MM cell proliferation and induce apoptosis.
, the study data identified GCK as a new target in RASMut MM cells, providing a theoretical basis for the treatment of RAS mutations in MM.
addition, GCK inhibitors may be an alternative to overcoming IMiD resistance in MM.
.