A GlaxoSmithKline experimental drug, GSK3052230, prevents tumor growth in mice carrying human mesothelioma tumors. The data supports ongoing investigations of the drug as a mesothelioma treatment.
The study, “Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230,” was published in the journal Oncotarget.
GSK3052230 prevents tumors by sequestering the molecule FGF (fibroblast growth factor), used by many tumors in the initial stages of growth and to maintain the tumor at later disease stages. Among other things, the molecule helps the tumor grow new blood vessels to support it with oxygen and nutrients.
While there are many different FGFs and four receptors, tumors tend to use the FGF receptor 1 (FGFR1). GSK3052230 is an engineered protein that uses part of the FGFR1 to trap FGFs, preventing them from binding to the receptor.
GSK3052230 does not bind with high affinity to the types of FGFs that act as hormones, and so its use is not linked to side effects usually seen with blockers of the receptor. Lab tests have shown that the compound effectively prevents tumor growth in other types of cancer, including lung and endometrial cancers.
A Phase 1 clinical trial (NCT01868022) is currently recruiting people with mesothelioma to study the drug in human patients. To explore the effects of GSK3052230 in mesothelioma, researchers at GlaxoSmithKline used mesothelioma cells grown in the lab and in mice growing mesothelioma tumors.
Researchers treated mice carrying two different mesothelioma tumors with three different doses of the drug. One of the tumors reacted to the two highest doses of GSK3052230, with tumor growth reduced by 57% and 78%, respectively. The other tumor was blocked only by the highest dose that prevented tumor growth by 50 percent.
Further analysis in lab-grown cells identified molecular events linked to tumor growth inhibition. Cell experiments also demonstrated that the drug was most effective in blocking the growth of tumors where high levels of FGF and FGFR1 were found.
In addition, GSK3052230 treatment led to a lower density of blood vessels inside a tumor, but oddly enough, this did not seem to impact the blood flow, highlighting the complex mechanisms of FGF actions in tumors.
Still, the researchers believe that the data presented in their study supports the ongoing clinical evaluation of GSK3052230 in previously untreated mesothelioma patients.
Given the correlation found between high levels of FGF/FGFR expression in antidrug effectiveness in mice, researchers will now retrospectively study tumor specimens from patients enrolled in the ongoing Phase 1 mesothelioma trial to look for correlations with response to therapy.