The melanoma field with dendritic roots.

Abstract

It has been over 8 years since the journal Pigment Cell Research incorporated melanoma into its name and broadened its catchment of research submissions. During that time, the melanoma field has made broad strides including the characterization of different genomic subsets of melanomas, understanding the role of the microenvironment in tumor progression, and demonstrating efficacy of targeted inhibitors and immune checkpoint blockade agents in advanced-stage melanoma patients. Indeed, one would be hard pushed to find a tumor type in which the advances have been so remarkable during this time period. The current treatment landscape for advanced-stage melanoma patients now offers a high chance for a durable response, a situation that few imagined possible at the start of 2008. While it is appropriate to laud these advances, the field must not rest on its laurels. The white paper, ‘The State of Melanoma: challenges and opportunities’, in this issue of PCMR is directed at continuing to push fronts in the melanoma field. As this field continues to explore high impact translational questions, one must not forget melanomas ‘dendritic’ roots in the pigment cell research field. Many of the current major questions within the melanoma field can be traced to seminal studies in pigment cell biology. One clear example of the influence of pigment cell research is MITF. This transcription factor was first identified as a mutated gene associated with loss of pigmentation but was more recently found to be amplified in melanoma and alterations in its expression linked to drug-resistant melanoma cell populations. Other transcription factors, FOXD3 and PAX3, that were originally studied for their role in the differentiation/dedifferentiation of neural crest cells, have also been associated with drug-tolerant states. It is now clear that many malignant traits in melanomas are modulated by melanocytic-lineage selective factors. In considering some of the critical questions posed in the white paper, it will be important to take into account the findings from the pigment cell developmental and disorders fields. Understanding mechanisms underlying cellular dormancy of melanoma cells, exploring factors that direct melanomas to metastasize to the brain and identifying determinants of response and resistance to immune checkpoint agents will be enriched by considering knowledge gained from studies in normal pigmented cells. Furthermore, models that have been used for years to visualize altered pigmentation of the skin and other tissues are now being modified/extended to measure melanoma growth in the context of therapeutic intervention and to visualize the dissemination of melanocytic cells even at the single-cell level. While PCMR offers one avenue to promote discussion across fields, we should take advantage of other opportunities. Cross attendance at international meetings of societies associated with the journal is a venue to exchange views. In the next 6 months, we look forward to meetings of the European Society for Pigment Cell Research (Milan, September), PanAmerican Society for Pigment Cell Research (Baltimore, October), and Society for Melanoma Research (Boston, November). At the funding level, there is a growing emphasis on team science collaborative awards from foundations as well as federal sources. Such efforts benefit from being cross-disciplinary, new initiatives involving multiple institutions. All these efforts should promote the bidirectional sharing of ideas, resources, and collaborations, and help investigators to continue to meet the challenges and opportunities that arise in the melanoma and pigment cell research fields.