The goal of Dr. Altiok’s research is to establish primary non-small cell lung cancer (NSCLC) xenografts to study pharmacodynamic profiles of tumors to predict and assess response to targeted therapy. His work also focuses on analyzing the link between G2 checkpoint control and sensitivity to histone deacetylase inhibitor (HDACi) therapy in NSCLC. He seeks to develop methods to analyze the efficacy of targeted agents in a NSCLC model using patients' tumor tissue obtained at the time of cancer resection. In primary NSCLC engrafts models Dr. Altiok and colleagues demonstrated that HDACi-induced cell death is closely associated with unscheduled mitotic entry. This effect appears to be mediated by activation of cdc2 kinase and inhibition of CHK1, a kinase with an integral role in the regulation of S and G2/M checkpoints and mitotic cell death. In ex vivo experiments with primary tumor cells obtained by FNAB they showed that the lack of cdc2 activation correlates with resistance to the cytotoxic effects of HDACis. Consistent with this observation, the data showed that a clinically relevant Wee1 inhibitor MK1775 that activates cdc2 has strong synergistic effect with the pan-HDAC inhibitor SAHA in NSCLC cells.In collaboration with Drs. Jhanelle Gray and Eric Haura, his laboratory team is analyzing molecular response to HDACi treatment in tumor FNAB material obtained from NSCLC and head and neck cancer patients enrolled in a phase I expansion trial. Additionally, they designed a phase I trial to test the clinical feasibility of MK1775 and SAHA combination treatment in NSCLC.