Pathogenesis of Merkel Cell Carcinoma

Despite a substantial research effort, the understanding of the molecular basis of MCC is still limited. Overexpression of the anti-apoptotic molecule bcl-2 was observed in three-fourths of MCC tumors in two independent studies [10, 21]. Inhibition of bcl-2 expression in vivo by antisense oligonucleotides in a SCID mouse/human tumor xenograft model resulted in tumor shrinkage [31]. The expression of this anti-apoptosis protein is a common finding in many cancers and suggests one of its mechanisms to avoid cell death; however, the same antisense oligonucleotides when tested in a phase II trial, demonstrated only a very limited, if any, efficacy in patients with MCC [32]. Moreover, bcl-2 overexpression does not illuminate the promitotic pathways that drive MCC.