Molecular pathogenesis and therapy innovation for Merkel cell carcinoma

National Institute Of Arthritis And Musculoskeletal And Skin Diseases

Investigators

Linked publications & trials

Abstract

To identify genetic alterations present in Merkel cell carcinoma, we have conducted molecular analyses of human tumors and cancer cell lines across multiple genome-wide platforms to assay gene expression, identify gene mutations, and characterize chromosomal alterations. These data are being analyzed to identify key driver alterations for this tumor. We are also generating mice where oncogenic modifications are carried out in specific skin lineages in an attempt to transform cells into Merkel cell carcinoma in vivo. In addition, we are developing and characterizing cancer cell lines of Merkel cell carcinoma for in vitro and xenograft studies. We are also developing clinical biomarkers for Merkel cell carcinoma. Work investigating the epigenetic alterations in Merkel cell carcinoma have led to interesting discoveries about the relationship between Merkel cell polyomavirus and the host cell that forms Merkel cell carcinoma. We have also developed a protocol for the clinical expansion of T lymphocytes that recognize Merkel cell polyomavirus tumor antigens as a potential cellular therapy for virus positive Merkel cell carcinoma. Finally, we are conducting high throughput small molecule and genetic knockdown screens to identify pathways important for tumor survival and identify novel treatments for Merkel cell carcinoma.