Dawid Grzela, Ewelina Stoczyńska-Fidelus, Anna Lenart, Marcin Pacholczyk, Cezary Tręda, Maciej Walczak, Marta Winiecka, Sylwester Piaskowski, Krystyna Hułas-Bigoszewska and Piotr Rieske

Celther Polska Sp. z o. o. Milionowa street 23; 90-364 Łódź, Poland

Abstract:

EGFR pathways are targeted by many new anticancer compounds.  Still, effects of those therapies are far from expectations.  Our goal is to develop new small compounds effectively blocking  pathways triggered by mutated EGFR.  Until now we have designed wide sets of small molecules for in vitro testing.  Schrodinger, and Discovery studio software  were used to design those molecules.  Putative inhibitors and activators of EGFR pathway were in vitro tested by means of X-Celligence, CT-Biostation and classical approaches such as Immunocytochemistry.  Apparently, we have noticed some paradoxical actions of activators and  inhibitors of EGFR pathways. For example we observed accelerated cancer cells proliferation thanks to inhibitors and cancer cells apoptosis thanks to activators of these pathways. Our results suggest that effects of anti EGFR pathways drugs  can be unexpected.  However, we can not exclude that observed effects are consequence of side effects of molecules designed by bioinformatics.

This work was supported by Polish Agency for Enterprise Development POIG. 01.04.00-10-037/11