Nevertheless in at least two MCC cell lines, the protein expression of Notch1, AKT, mTOR, and STAT3 was downregulated by GP-2250, thus indicating that altered Notch and PI3K/AKT/mTOR pathways in virus-negative MCC can effectively be addressed by the novel substance GP-2250. This evidence concerns the gene NOTCH1 and Merkel cell skin cancer.