PI3Kd Inhibition Modulates the Innate Inflammatory Response in Pancreatic Ductal Adenocarcinoma and Normalizes Aberrant Metabolism Associated with Cachexia

PDAC is an inflammatory disease in urgent need of effective therapeutic intervention. The PI3K p110d isform inhibition resulted in sustained survival rarely seen in KPC mouse model of pancreatic cancer. The single agent therapy significantly decreased tumor burden, differentially regulated tumour inflammatory and metabolic transcirptome profile and normalized muscle metabolic response associated with cachexia. Overall design: Tumour bearing KPC mice were treated with either vehicle or PI3K p110d inhibitor for 2 weeks. Whole tumour was then harvested and RNA sequencing was perfomred on total RNA. For immature myeloid RNA seq, cells were sorted from the spleen of tumor bearing mice treated with vehicle or drug for 14 days. Total RNA was then isolated and sequenced on an NGS platform.