MTI-101 for the treatment of EGFR driven lung cancer

Lung cancer continues to be the most deadly disease and new treatment strategies are required to improve patient outcomes.  Screening 24 molecularly defined lung cancer cell lines we found that MTI-101 demonstrated increased activity EGFR and RTK driven tumors compared to KRAS or BRAF driven tumors.  We hypothesis that RTK driven calcium signaling lowers the threshold for MTI-101 induced cell death.  Treatment of EGFR driven tumors is limited by the rapid emergence of adaptive and acquired resistance. Importantly, MTI-101 retains activity in acquired Erlotinib resistant cell lines.  The goal of this project is i) use genetic techniques to define the dependency of MTI-101 on EGFR driven tumors; ii) determine the activity of MTI-101 using EGFR driven in vivo models iii) define the therapeutic window iii) determine PK and validate PD markers using in vivo models and iv) further delineated the mechanism of action of this novel class of compounds using resistant models developed in vitro and in vivo

 This project is supported by the CTSI pilot award program