Given the differential expression of PI3K isoforms in MCC, we examined antitumor efficacy of four different FDA-approved PI3K isoform-specific inhibitors (idelalisib, copanlisib, duvelisib, and alpelisib) as well as AZD8186, a dual PI3K-β/δ inhibitor currently in advanced clinical development. This evidence concerns the gene PIK3CA and Merkel cell skin cancer.