Abstract A08: Modeling melanomagenesis

Abstract

Abstract Despite recent advances in therapy, cutaneous melanoma remains a deadly form of skin cancer. Ultraviolet radiation is a known risk factor that can be reduced by the use of sunscreen; nevertheless, melanoma incidence continues to rise. Determining how a cell that contains all the mutations required for cancer resists forming a tumor could suggest novel means of prevention. Conversely, understanding an identical cancer cell of origin that has switched to a proliferative expansion state can provide invaluable insight into tumor initiation. We have generated a method of inducing melanoma from melanocyte stem cells in a spatially specific manner by altering the exterior environment, in the context of a previously established genetically engineered mouse model of melanoma. Specifically, exposure to ultraviolet radiation B can provide a proinflammatory microenvironment that stimulates this switch from a quiescent cancer cell of origin to a proliferative cancer cell. Moreover, this model shows tumor development from the interfollicular epidermis, similar to human melanoma initiation and progression. This represents an evolution from previous mouse models of melanoma and presents a new method that can be exploited for stage-specific precision targeting for both initiation prevention and progression intervention. Citation Format: Hyeongsun Moon, Leanne Donahue, Andrew C. White. Modeling melanomagenesis [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A08.