Abstract
e13559 Background: Current development is focused on agents targeting the RAF-MEK-ERK and PI3K-AKT-mTOR pathways. Combinations of these agents may address causes of de novo resistance. Identifying patients (pts) most likely to benefit from these combinations is important. Methods: A panel of 20 cell lines (5 BRAFM, 5 KRASM, 5 PIK3CAM and 5 BRAF/PIK3CA/KRASWT) were exposed to MEK and/or AKT inhibitors and evaluated for inhibition of pathway signaling and cell growth. Inhibition of signaling output of the RAF-MEK-ERK (p-ERK) and PI3K-AKT-mTOR (p-S6) pathways was quantified by ELISA. Growth inhibition was determined using sulforhodamine B assay. Based on the results of preclinical experiments, at our center we prioritized enrolling pts with RAS mutant tumors (including ovarian cancer and non-small cell lung cancer [NSCLC]) into an ongoing phase 1b clinical trial (CMEK162X2109) evaluating the combination of MEK inhibitor binimetinib (MEK162) and the PI3K-α inhibitor BYL719 in pts with RAS and RAF mutant tumor...
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
