Frontiers in pigment cell and melanoma research

Abstract

Summary In this perspective, we identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology. Significantly, this document encapsulates important advances in melanocyte and melanoma research including emerging frontiers in melanoma immunotherapy, medical and surgical oncology, dermatology, vitiligo, albinism, genomics and systems biology, epidemiology, pigment biophysics and chemistry, and evolution.

Concurrent Targeting of Glutaminolysis and Metabotropic Glutamate Receptor 1 (GRM1) Reduces Glutamate Bioavailability in GRM1+ Melanoma

“…Metabotropic glutamate receptor 1 (GRM1) is an oncogenic driver in the neuroectodermal-derived lineage of melano-cytes (45). Aberrant glutamatergic signaling activates mitogenesis and melanomagenesis independent from canonical mitogen-activated protein kinase signaling (4).…”

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials

“…Tumor promotion involves the accumulation of additional mutations and often occurs over many years. 3,4 UVR also is involved in the promotion of melanoma. Progression refers to the final development of a tumor with invasive potential, which also may involve the acquisition of new mutations, epigenetic modifications, and loss of immune control of early oncogenic cellular changes.…”

“… Precis: In this work, experts from the national Melanoma Prevention Working Group, 156,157 comprised of National Cancer Trials Network participants, discuss mechanisms of action, preclinical data, epidemiologic evidence, and results from available clinical trials for the most promising melanoma chemoprevention agents. Furthermore, the work provides an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.…”

Targeting Glutamate Metabolism in Melanoma

“…In case MAPK driver mutations are lacking, the genotype is classified as NF1/NRAS/BRAF triple negative or triple wild-type subtype and remains without actionable molecular targets. Overcoming the lack of molecular targets of this subtype has been identified as one of the prime goals of the melanoma and pigment cell research community 14 . In order to understand and quantify the metabolic phenotype of GRM1-activated (GRM1 + ) cells, we profiled an isogenic cellular melanoma model by GCMS (Figure 1).…”

“…Elevated tumor expression of GRMs has been reported not only in central nervous system tumors where glutamate is abundant, but also in melanoma, breast, and prostate cancers [10][11][12][13] . The neuroectodermal origin of melanocytes, pigment producing cells that migrated and differentiated from the neural crest into the skin, might be of particular relevance in malignant melanoma 14 . Metastases to the central nervous system are among the most common and lethal complications of metastatic melanoma.…”