Blocking Polo-like kinase 1 may stop metastatic breast cancer cells from growing in the brain

Polo-like kinase 1 (Plk1) mRNA expression was significantly increased in brain metastases compared to systemic metastases (P = 0.0018).

• Plk1 is primarily expressed in dividing cells and is upregulated in many tumors, making it a potential therapeutic target.
• The selective Plk1 inhibitor, GSK461364A, was shown to have substantial uptake in normal rodent brain tissue.
• In a breast cancer brain metastatic model, GSK461364A treatment at 50 mg/kg inhibited the development of large brain metastases by 62% (P = 0.0001) and prolonged survival by 17%.
• GSK461364A also sensitized tumor cells to radiation-induced cell death in laboratory tests.
• In a study of 41 primary breast tumors and matched brain metastases, p53 expression was increased in 61% of metastases, suggesting a potential link to sensitivity against Plk1 inhibition.

Simplified