- ESE1/ELF3 and NF-kB are co-activated in selected prostate tumors and associated with adverse prognosis in prostate tumors, according to researchers at the IOR (Switzerland).
- EC-70124, a kinase inhibitor being developed at EntreChem SL, has shown efficacy when administered orally in a murine model of prostate cancer whose malignant phenotype depends on ESE1/ELF3 and NF-kB co-activation.
The results of a collaborative research from EntreChem SL (Oviedo) and Institute of Oncology Research (IOR, Bellinzona, Switzerland) focused on searching for a new strategy for Prostate Cancer, globally the sixth leading cause of cancer-related death in men (second in the United States), has been presented in a poster in the American Association for Cancer Research meeting (AACR 2013) held on April 6th-10th 2013 in Washington D.C.
The research, directed by Drs. Giuseppina Carbone, Group Leader for the Prostate Cancer Biology program and Carlo Catapano, Director of the Tumor Biology and Experimental Therapeutics Program, both at IOR, focuses on prostate cancer, where the ETS family transcription factor ESE1/ELF3 is overexpressed, concurrently with activation of NF-kB. This work shows that ESE1/ELF3 exerts oncogenic functions and is an important link between inflammatory signaling and prostate cancer progression. Moreover, this expression pattern was associated with significantly reduced overall survival and increased disease recurrence, making this subset of tumors a high medical need within the prostate cancer space.
EC-70124 inhibits NF-kB reporter activity in prostate cancer cells and reduced phosphorylation of IkB, both in vitro and in vivo. Expression of genes induced by ESE1/ELF3 and NF-kB, cell migration and proliferation were significantly reduced by EC-70124 selectively in ESE1/ELF3 expressing cells. Moreover, EC-70124 reduced growth of DU145 prostate tumor xenografts, with constituvely high expression of ESE1/ELF3 and NF-kB, in immunodeficient mice when administered orally daily for 2 weeks at doses well below toxic levels.
Collectively, this study provides a mechanistic link between inflammation and prostate cancer progression and suggests new tools for patient stratification and design of context-dependent strategies for a subset of prostate cancer patients with clinically aggressive and high risk tumors marked by ESE1/ELF3 and NF-kB activation. As seen in prostate tumors, a similar activation loop between ESE1/ELF3 and NF-kB might exist in other tumor types, which might be highly sensitive to treatment with molecules like EC-70124.
The inhibitor EC-70124, is currently undergoing preclinical development by EntreChem SL (therefore not yet available for human assays). EC-70124 is a hybrid natural product obtained from genetically modified bacteria by combinatorial biosynthesis.
EntreChem SL is a spin off company created from research developed in the University of Oviedo, and its shareholders include, aside from the original co-founders, local industry companies such as Industrial Química del Nalón, Alvargonzález SA and Alimerka. Private financing is complemented by regional, national and european public programs like NEOTEC program (MICINN), Genome Spain Foundation, FICYT, IDEPA, SRP and the Seventh Framework Programme from the European Union.
More information:
Dr. Giuseppina Carbone: pina.carbone@ior.iosi.ch, +41 91 820 0366
Dr. Carlo Catapano: carlo.catapano@ior.iosi.ch, +41 91 820 0365
Dr. Francisco Morís Varas: fmv@entrechem.com, +34 985 259 021
and also:
IOR: http://ior.iosi.ch
EntreChem SL: www.entrechem.com
