Niraparib treatment of metastatic melanoma in vivo

Twenty four NSG mice (3 groups, 8 mice/group) were injected subcutaneoulsy with melanoma PDX cells (MM425X). When tumors reached 100mm3, daily i.p. injections of 25mg/kg niraparib were administred to the tumor bearing mice for 30 days. The treatment resulted in significant anti-tumor effects against MM425X. To determine the transcriptomic profiles altered following niraparib treatment, RNA-Seq was performed in MM-425 tumors from three mice treated with niraparib compared with three mice treated with vehicle. To that end, 3 tumors/group (vehicle vs Niraparib treated) were harvested for RNA extraction. RNA extraction from flash-frozen tissue samples was performed as previously described (Olsson et al., 2016, Salomonis et al., 2010, Soroceanu et al., 2013). Total RNA was extracted from PDX tumor tissues using the RNeasy tissue kit (Qiagen) after tissue disruption using ruptor disposable probes and the concentration measured by Qubit RNA HS Assay Kit (ThermoFisher Scientific). RNA-Seq was performed from ~500ng of total RNA processed using TruSeq polyA selection, at a target depth of 40 million paired-end, stranded reads on an Illumina 2500 Overall design: 6 samples were anlyzed, 3 from vehicle treated mice and 3 from mice treated with Niraparib