A new study reports that combining imatinib with CX-4945, which inhibits casein kinase 2 (CK2), resulted in synergistic anticancer effects in gastrointestinal stromal tumors (GISTs).

The study, published in Clinics and Research in Hepatology and Gastroenterology, also reported that the combination treatment had a stronger anticancer effect than monotherapy and that the treatment worked via inhibition of the PI3K/AKT pathway.

“Our results showed that CK2 was highly expressed in GIST biopsies, and inhibition of CK2 resulted in a decrease in cell viability and increase in apoptosis of GIST cells,” the authors wrote. “Moreover, the combination treatment with CX-4945 and imatinib resulted in a more significant decrease in cell viability and decrease in cell apoptosis compared with mono-treatment.”


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The research team assessed 46 pairs of GIST biopsies and normal tissues and found that the expression of the CK2 protein was significantly increased in the biopsies, as has been reported for other cancers and in cases of tumor progression. Inhibition of CK2 decreased cell viability and increased apoptosis of GIST cells.

Furthermore, CK2 inhibition synergistically increased apoptosis and the inhibition of cell proliferation induced by imatinib.

The authors attribute the synergistic effects to downregulation of the PI3K/AKT pathway, which has been shown to be associated with cell proliferation, survival, differentiation, and apoptosis, as well as the progression of GISTs specifically. Here, the results indicate that the combined treatment of CX-4945 and imatinib downregulated the PI3K/AKT pathway to a greater degree than single-agent treatment, and the activation of the PI3K/AKT pathway reversed the effects of the combined treatment.

The authors expect their results to help reveal new directions for novel therapeutic strategies for GIST.

Reference

Zhou L, Wang H, Liu H, et al. The synergistic therapeutic effect of imatinib and protein kinase CK2 inhibition correlates with PI3K-AKT activation in gastrointestinal stromal tumors. Clin Res Hepatol Gastroenterol. Published online February 17, 2022. doi:10.1016/j.clinre.2022.101886