pf-3758309 and Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most prevalent pediatric soft-tissue sarcoma. Multimodal treatment, including surgery and traditional chemotherapy with radiotherapy, has contributed to improvements in overall survival rates. However, patients with recurrent or metastatic disease have 5-year survival rates of less than 30%. One reason for the lack of therapeutic advancement is identification and targeting of critical signaling nodes. p21-activated kinases (PAK) are a family of serine/threonine kinases downstream of multiple critical tumorigenic receptor tyrosine kinase receptors and oncogenic regulators, including IGFR and RAS signaling, that significantly contribute to aggressive malignant phenotypes. Here, we report that RMS cell lines and tumors exhibit enhanced PAK4 expression levels and activity, which are further activated by growth factors involved in RMS development. Molecular perturbation of PAK4 in multiple RMS models

Topics: Acrylamides; Aminopyridines; Animals; Apoptosis; Biomarkers, Tumor; Cell Movement; Cell Proliferation; Child; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; p21-Activated Kinases; Pyrazoles; Pyrroles; ras Proteins; Rhabdomyosarcoma; Tumor Cells, Cultured; Xenograft Model Antitumor Assays