Skin cancer has always been and remains the leader among all tumors in terms of occurrence.,One of the main factors responsible for skin cancer, natural and artificial UV radiation, causes the mutations that transform healthy cells into cancer cells.,These mutations inactivate apoptosis, an event required to avoid the malignant transformation of healthy cells.,Among these deadliest of cancers, melanoma and its ‘younger sister’, Merkel cell carcinoma, are the most lethal.,The heavy toll of skin cancers stems from their rapid progression and the fact that they metastasize easily.,Added to this is the difficulty in determining reliable margins when excising tumors and the lack of effective chemotherapy.,Possibly the biggest problem posed by skin cancer is reliably detecting the extent to which cancer cells have spread throughout the body.,The initial tumor is visible and can be removed, whereas metastases are invisible to the naked eye and much harder to eliminate.,In our opinion, antisense oligonucleotides, which can be used in the form of targeted ointments, provide real hope as a treatment that will eliminate cancer cells near the tumor focus both before and after surgery.
Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence.,The understanding of the molecular carcinogenesis of MCC is limited.,Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC.,Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples.,Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV).,Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT.,We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations.,Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent.,MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002.,This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients.