|EntreChem's kinase inhibitor shows potential for treatment of head and neck cancer
March 26th, 2012 - Oviedo (Spain)
||The PI3K/Akt/PTEN molecular pathway is frequently mutated in this type of tumor, where activation of the Akt kinase is a poor prognosis factor, according to researchers at CIEMAT.
||EC-70124, a kinase inhibitor under development at EntreChem SL, has shown efficacy in a murine model of Head & Neck cancer that expresses a permanently active form of the Akt1 kinase together with loss of Trp53.
The results of a public-private collaborative research from EntreChem SL (Oviedo) and CIEMAT (Research Center for Energy, Environment and Technology, in Madrid) focused on searching for a new strategy for Head and Neck Squamous Cell Carcinoma, one of the 10 most common cancers worldwide, has been presented in a poster in the Cold Spring Harbor Symposium "PTEN Pathways and Targets" held on March 13th-16th in New York.
The research, directed by Dr. Jesús Paramio, Head of the Molecular Oncology Unit at CIEMAT, makes use of a HNSCC mouse model, myrAkt;Trp53Epi, which expresses a permanently active form of the Akt1 kinase together with loss of Trp53 expression in the basal layer of stratified epithelia. Oral tumors in these animals have a high incidence and they are phenotipycally similar to human HNSCC.
EC-70124 reduces oral keratinocyte cell viability in a dose-dependent manner, and it specifically affects myrAkt;Trp53Epi protumoral cells, both in vitro and in vivo. EC-70124 regulates PI3K/Akt/PTEN pathway in myrAkt;Trp53Epi oral keratinocytes. The molecule EC-70124, a selective kinase inhibitor, reduces myrAkt;Trp53Epi tumor growth in immunodeficient mice administered intraperitoneally at doses well below toxic levels in mice.