MerTK inhibition slowed growth of various tumors
Tumor growth was reduced in mouse models of breast cancer, colon cancer, and melanoma after the protein MerTK was removed from immune cells, researchers reported.
MerTK belongs to a family of receptor tyrosine kinases that are widely expressed in many epithelial tissues and in cells of the immune, nervous, and reproductive systems, explained H. Shelton Earp III, MD, of the UNC [University of North Carolina] Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina, and fellow investigators in The Journal of Clinical Investigation. MerTK has a role in tyrosine kinase activation and is expressed or overexpressed in many hematologic and epithelial malignant cells. The expression of MerTK correlates with poor prognosis or chemoresistance in some types of tumors.
Earp's group found that removing MerTK from immune cells decreased the growth of breast and colon tumors as well as melanoma in mice. Tumors formed with an average latency of 28 days in mice still producing MerTK, but latency was delayed in the mice with no MerTK: Tumors remained unpalpable in 70% of the MerTK-negative mice throughout the entire 198-day study period.
Mice that were able to produce MerTK to a certain extent, but not fully, formed tumors with an average latency of 49 days, which was intermediate between the other two sets of mice. According to the study authors, this suggests a dose-dependent relationship between MerTK signaling in the stromal environment and tumor growth.
Removal of MerTK also reduced the release of molecules associated with inflammation.Earp and team concluded that MerTK inhibition in the tumor microenvironment may have clinical benefit, stimulating antitumor immune responses or enhancing immunotherapeutic strategies.