Synergistic targeting of the PI3K/mTOR and MAPK/ERK pathways in Merkel cell carcinoma.

ABSTRACT: Merkel cell carcinoma (MCC) is an aggressive type of skin cancer, which is caused either by integration of the oncogenic Merkel cell polyomavirus (MCPyV) or by accumulation of UV-light induced mutations. Since the response to immune-checkpoint inhibitors is limited, new therapeutic agents need to be explored. Previous studies have shown that MCC cell lines and xenografts are sensitive to MLN0128, a dual mTOR1/2 inhibitor. Prompted by these results and considering that the PI3K/mTOR and MAPK/ERK pathways are the most commonly deregulated pathways in cancer, the combination of MLN0128 with the MEK1/2 inhibitor trametinib was investigated. Importantly, the combined targeting showed to be synergistic in MCC cell lines and induced alterations in the protein levels of downstream elements of the

SUBMITTER: Temblador A 

PROVIDER: S-EPMC9449649 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature