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Oncotarget is a multidisciplinary traditional journal with free-access. Oncotarget mission is to make scientific results rapidly and widely available. The journal helps all researchers contribute to the progress of science.

EC-70124 is a hybrid natural product obtained by combinatorial biosynthesis from genetically modified bacteria,  and are currently in advanced preclinical studies by EntreChem S.L. (not available yet for trials in humans).

EntreChem SL is a Spanish spin off from the University of Oviedo, and its shareholders include original co-founders and local family offices. Private financing is complemented by public funds from MINECO, Genome Spain Foundation (now FECYT), FICYT, IDEPA, SRP and the 7FP and H2020 from the European Union.

More information:

Dr. Alberto Ocaña: albertoo@sescam.jccm.es
+34 967 597 100, ext. 37087

Dr. Atanasio Pandiella: atanasio@usal.es
+34 923 294 815

Dr. Francisco Morís: fmv@entrechem.com
+34 985 259 021

and also:

CHUA:
www.chospab.es/investigacion/oncologia_traslacional/intro.htm

CIC:
www.cicancer.org

EntreChem SL:
www.entrechem.com
New EntreChem publication in Oncotarget describing activity of EC-70124 in colorectal cancer

December 21th, 2015 - Oviedo (Spain)

•  Activated kinases were identified by using phosphokinase arrays with human colorectal tumor samples, including the Epidermal Growth Factor Receptor (EGFR), components of the PI3K/mTOR pathway (AKT and S6), and SRC, among others.

EC-70124, a kinase inhibitor, shows high in vitro antiproliferative activity as well as cell migration inhibition. Major effects are related to targeting of the PI3K/mTOR pathway and SRC. The combination with standards of care is synergistic in vitro, and also reduced tumor growth in vivo and inhibited pS6 in the implanted tumors,  offering opportunities for combination therapy with drugs currently in clinical use.

The results of a collaborative research from EntreChem SL (Oviedo), the Translational Cancer Research Unit at Albacete University Hospital, CHUA (Albacete, Spain)  and the Translational Oncopharmacology Unit of CIC (Salamanca, Spain) focused on searching new strategies for colorectal cancer, which accounts for approximately 9% of all cancer incidence, have been published in the journal Oncotarget.

The research, directed by Dr. Alberto Ocaña (CHUA), with participation from Dr. Atanasio Pandiella (CIC) focuses on receptor tyrosine kinases (RTKs) downstream signaling pathways involved in the regulation of proliferation and survival, like PI3K/mTOR, and SRC.

EC-70124 shows in vitro antiprolife rative and antimigration effects mediated by simultaneous inhibition of the PI3K/mTOR signaling pathway and SRC, and also by DNA damage induction, causing cell cycle arrest on G2/M. EC-70124 in vivo, when dosed intravenously, significantly delayed tumor growth without signs of toxicity, and treatment with the drug reduced pS6 levels at different timepoints, confirming the effect of the drug in the PI3K/mTOR pathway.

Most current therapeutic strategies in oncology are based on drug combinations, therefore identification of synergistic interactions between targeted agents and chemotherapies is a main goal. Studies in combination with standards of care showed synergy with chemotherapeutic agents like irinotecan, oxaliplatin and 5-fluorouracil raising the possibility to explore these combinations in the clinical setting.

For full details, see: Serrano-Heras G et al, Phospho-kinase profile of colorectal tumors guides in the selection of multi-kinase inhibitors. Oncotarget  2015; 6(31): 31272-83.

The prognosis of colorectal cancer is poor due to the limited therapeutic options and the lack of specific targeted agents.  The multitargeted kinase inhibitor EC-70124 shows activity in RTKs and their downstream routes, and combines synergistically with several current standards of care, so EC-70124 represents an opportunity to explore a polypharmacology approach in colorectal cancer.


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