A novel Pik3ca-driven mouse model and syngeneic cancer cell line for the preclinical testing of targeted and immune therapies for anal squamous cell carcinoma (ASCC)

Abstract

Abstract Although many patients with localised anal squamous cell carcinoma (ASCC) initially achieve a complete response with standard chemoradiotherapy, those with persistent, relapsed or metastatic disease (35% of all patients) have limited treatment options and poor outcomes. Recent genomic profiling studies have identified PIK3CA as the most frequently mutated gene in anal cancers. Amplification of the PIK3CA gene and mutations in other PI3K pathway genes, have also been detected providing a strong rationale for targeting the PI3K pathway in these tumours. Similarly, the finding that many ASCC tumours express immune checkpoint receptors including PD-L1, has focussed att..