LU 2017-124
INVENTORS
SHORT DESCRIPTION
Embryonal tumors such as malignant rhabdoid tumors (MRTs) are aggressive and frequently metastatic embryonal tumors of infancy. However, available therapies often elicit modest anti-tumor response leading to poor survival, or induce highly toxicity in patients of young age. Utilizing CRISPR/Cas9, Northwestern researchers screened a library of kinases and identified polo-like kinase 4 (PLK4) as a key mediator that is upregulated in tumor progression. A small molecule inhibitor of PLK4, CFI-400945, demonstrated cytotoxicity on rhabdoid tumor cells leading to reduced cell survival, suppressed cell proliferation, and decreased cell migration and invasion. Treatment with CFI-400945 did not affect the migration of non-neoplastic human fibroblasts or result in zebrafish larvae death, suggesting low levels of toxicity, an important feature for use in a young pediatric patient population. Therefore, PLK4 inhibitors such as CFI-400945 appear to be effective and safe therapeutics for rhabdoid tumors and other embryonal tumors of the central nervous system.
PUBLICATION
Sredni, S.T. et al. (2017) Inhibition of polo-like kinase 4 (PLK4): a new therapeutic option for rhabdoid tumors and pediatric medulloblastoma. Oncotarget, 8, 111190-111212.
Sredni, S. T. et al. (2017) A functional screening of the kinome identifies the Polo-like kinase 4 as a potential therapeutic target for malignant rhabdoid tumors, and possibly, other embryonal tumors of the brain. Pediatric Blood Cancer, 64, e26551.
Sredni, S. T. et al. (2017) The polo-like kinase 4 gene (PLK4) is overexpressed in pediatric medulloblastoma. Child's Nervous System, 33, 1031.
IP STATUS
A US utility patent (US-11197863) has been issued.