|EntreChem's developmental drug opens the door to a new strategy for glioblastoma
May 9th, 2011 - Oviedo (Spain)
||Glioblastoma initiating cells activate NFkB cell signaling pahtway to avoid terminal differentiation, according to researchers in Hospital Valdecilla.
||EC-70124, an inhibitor of NfkB pathway under development at EntreChem SL, has shown efficacy in murine models of glioblastoma.
A multidisciplinar research team from EntreChem SL (Oviedo), Valdecilla Hospital (Santander), University of Cantabria (Santander) and Universiy of Navarra´s CIMA (Center for Applied Medical Reseach, Pamplona) has developed a new strategy for glioblastoma, the most common and aggressive type of brain tumor in adults, according to results published by the journal Oncogene, one of the most prestigious in the world for cancer research.
The inhibitor EC-70124, discovered by the team of Prof. José Antonio Salas, from the Department of Microbiology of the University of Oviedo, is being developed by EntreChem SL, and it is currently undergoing preclinical development (therefore not yet available for human assays). EC-70124 is a natural product obtained from bacteria, which have been genetically modified to obtain this analog.
The research, directed by Dr. José Luis Fernández-Luna, Molecular Genetics Unit coordinator, and Dr. Alfonso Vázquez-Barquero, Neurosurgery Department chairman at the Valdecilla Hospital, makes use of patient biopsies to isolate glioblastoma initiating cells (sometimes called cancer stem cells). These initiating cells are radio- and chemotherapy resistant, and they are considered responsible for tumor recurrence. The strategy exploited by the researchers, consists in forcing the entry of differentiating cancer stem cells into sensescence, a non-viable state that leads to cell death, exhausting the source of tumor cells.
Blockade of NFkB pathway drives differentiating glioblastoma initiating cells (GICs) into a senescence stage, both in vitro and in vivo. The molecule EC-70124, a selective inhibitor of IKKb kinase (and therefore of NFkB), administered intravenously to mice xenografted with GIC-derived tumors (produced by CIGs implanted in the brain of the mice) induced senescence in tumor cells. However, ther rest of the brain structures remained unaltered, suggesting the compound acts selectively in tumor tissue. Mice studies have been conducted in collaboration with the group of Dr. José Angel Martínez Climent (CIMA) and Dr. Miguel Lafarga, Mª Teresa Berciano and Iñigo Casafont (University of Cantabria).