PHLDA1 mediates drug resistance in receptor tyrosine kinase driven cancer

Mutations or amplifications of receptor tyrosine kinases (RTKs) are common in many cancers. Given the emergence of small molecule inhibitors specific to RTKs, these signalling cascades are attractive therapeutic targets. However, compensatory and adaptation mechanisms limit the clinical utility of compounds that target nodes in RTK networks. Here we show that PHLDA1 down-regulation is critical to acquisition and maintenance of drug resistance in RTK-driven cancer. Total RNA obtained from cell lines resistant to small molecule FGFR inhibitors AZD4547 or PD173074 were profiled together with RNA from the parental cell line (MFE-296).