Melanoma Disease-Oriented Team (MDOT)

The Melanoma Disease-Oriented Team (MDOT) is committed to maximizing and integrating melanoma-related research at the University of Utah and HCI. To accomplish this we are bringing together individuals involved in: 1) clinical and translational research within the Melanoma & Cutaneous Oncology multidisciplinary group (MDG), 2) translational and population science research, and 3) melanoma-associated basic research within the Cancer Center.

Overview of Projects

MDOT members have been actively engaged throughout the year in weekly tumor board/Research-In-Progress meetings, seminars, and ongoing collaborative projects. A long term goal of the Melanoma DOT is development of mutli-investigator projects and as such we have encouraged collaborative projects. These include but are not limited to: Immunotherapeutic approaches for the treatment of melanoma; Targeting proteins involved in melanoma invasion and metastasis; Identification of novel melanoma susceptibility genes; and development of novel models of melanoma. One of these models, referred to as patient-derived xenografts (PDX), is at the leading edge of cancer drug development, and has emerged as a new approach for preclinical testing of novel anticancer agents.

Although the feasibility of establishing PDX models of melanoma was demonstrated decades ago (1, 2), there have been relatively few studies characterizing whether melanoma PDX models preserve key features of the original patient tumor, which include histology, genomic characteristics, heterogeneity, drug responsiveness, and patterns of metastasis. We have generated several melanoma PDX models and the majority have developed distant metastases. The distribution of common mutations in these models matches the averages reported within patient tumors [i.e., 40% contain mutant BRAF, 12% mutant NRAS, 8% mutant c-KIT, and 40% are triple negative (wild-type for BRAF, NRAS, and c-KIT)]. An important question regarding PDX model stability is whether the process of engraftment and expansion changes the genetic features of the tumors. Recent technological advances in Next Generation Sequencing platforms enable the determination of genetic alterations rapidly and at reasonable cost. Identifying and characterizing the genomic signature of each individual patient tumor is also likely to provide unique insights into specific molecular mechanisms of survival and therapy resistance present in that particular tumor and suggest more directed strategies for improved tumor killing and patient survival.