Value Proposition
· The first orthotopic model of acral melanoma (AM) that replicates the anatomical, transcriptional, and metastatic hallmarks of human disease.
· Replicates the plasticity of AM-specific cell states, which has not been demonstrated in any other orthotopic model of AM.
· Demonstrates that the microenvironment of plantar skin instructs melanoma cell behavior, overriding cell-intrinsic programming.
· Identifies a novel stiffness-activated signaling pathway [FAK–SRC YAP → cathepsin K] that drives metastasis.
Unmet Need
· Acral melanoma disproportionately affects patients of color and occurs on volar surfaces such as the soles and palms.
· Despite its aggressive nature and < 16% five-year survival rate in metastatic cases, AM lacks any approved targeted therapies or model systems.
· Current preclinical models—typically involving flank implantation—fail to replicate the unique biological context of volar skin, leaving a major gap in understanding AM pathogenesis and therapeutic vulnerabilities.
· Therefore, there is a strong need for a model of AM that accurately replicates the anatomical, transcriptional, and metastatic hallmarks of human disease.
Technology Description
· Researchers at Johns Hopkins have developed an orthotopic model of acral melanoma metastasis by implanting melanoma cells (mouse or human origin) into the plantar skin of mice.
· This implantation resulted in dramatic increase in lung and brain metastasis, enhanced tissue invasion and remodeling, and microenvironmentally induced transcriptional reprogramming.
· The biomechanical property of the plantar dermis also was found to activate a signaling cascade that drives upregulation of a collagen-degrading enzyme necessary for efficient metastasis.
