Identifying kinases that drive metastasis

Identifying kinases that drive metastasis

Metastatic prostate cancer is a fatal disease with few therapeutic options. Although mutationally activated kinases have been successful therapeutic targets for multiple types of cancer, genetic aberrations of kinases are rare in prostate cancer. However, evidence suggests that nonmutated kinases play a role in the development of metastasis.

Scientists developed an in vivo screen to identify wild-type kinases that can drive prostate cancer metastasis. Using genomic, transcriptomic, and phosphoproteomic databases, the authors studied 125 candidate kinases.

Kinases were overexpressed in a mouse prostate cell line and injected intravenously into immunodeficient mice. Twenty of these kinases caused metastases to develop in mouse lungs.

To determine which kinases are capable of driving metastasis in human cells, all 20 kinases were expressed in a nonmalignant human prostate cell line and separately injected into immunodeficient mice.

Five kinases, including MERTK, NTRK2, and all three RAF family members, drove the formation of bone and visceral metastases in mice. Histological analysis of tissue from human prostate cancer patients showed enhanced expression of these kinases in metastasis samples.

The results suggest that wild-type kinases may be potential therapeutic targets for metastatic prostate cancer, according to the authors.