UCLA researchers in the Department of Chemistry & Biochemistry, Molecular & Medical Pharmacology, and Neurology have discovered novel anti-tumor compounds for treatment of brain cancer.
Glioblastoma (GBM) is a devastating form of brain cancer with 12k new diagnoses each year in the United States and an average survival time of only 15 months after diagnosis. In 60% of these cancers, there are mutations in the epidermal growth factor receptor (EGFR) gene, presenting an effective target for anti-GBM therapies. However, many conventional EGFR tyrosine kinase inhibitors (TKIs) have failed in clinical trials, many due to insufficient transport across the blood-brain barrier (BBB). Potent EGFR inhibitors that are able to be transported across the BBB could have a significant impact on the effective treatment of GBM.
Professor Nathanson and coworkers have developed a novel series of compounds that exhibit very high brain penetration while also potently inhibiting tumor cell growth. While conventional TKIs have low brain to plasma ratios of 0.1, these compounds demonstrate excellent transport across the blood-brain-barrier, with a brain to plasma ratio of over 1.0. Additionally, lead compounds demonstrate similar or better potency compared to FDA-approved tyrosine kinase inhibitors such as Erlotinib, Gefitinib, or Lapatinib.
Compounds have been synthesized, their brain to plasma ratio has been determined, and potency has been assessed.
Tyrosine kinase inhibitor, cancer, glioblastoma, therapeutic, blood-brain-barrier