SYMPOSIUM ON SOLID TUMORSMalignant Melanoma in the 21st Century: The Emerging Molecular Landscape
Section snippets
CELL CYCLE CHANGES IN MELANOMA
The cellular cycle of growth and division (the cell cycle) is a carefully orchestrated sequence of events influenced by many factors, including the general state of cellular differentiation, activation of cell surface receptors, availability of nutrients, and level of cellular stress (eg, DNA damage). Almost all these factors lead to changes in cell-signaling patterns that ultimately converge on a set of molecularregulators of cell cycle progression—cyclins, cyclin-dependent kinases (CDKs), and
CELL SIGNALING CHANGES IN MELANOMA
Key signaling pathways that are important in melanoma and that represent potential novel therapeutic targets have been identified, and their regulatory mechanisms are beginning to be understood. The processes that are important in the development and progression of melanoma can be divided into the following categories: cellular proliferation, prosurvival signaling, growth factor receptor activation, differentiation regulation, cell adhesion, and migration.
THE GENOMICS OF MELANOMA
Recent advances in high-resolution genome-wide molecular techniques have greatly increased our ability to examine and understand molecular changes in cancer, including melanoma. The essence of these methods lies in the inherent property of DNA strands to form a duplex when two complementary DNA strands meet. This quality was exploited for design of DNA array platforms capable of measuring global changes in gene expression levels (ie, gene expression profiling), changes in gene copy number (eg,
UVEAL MELANOMA
Uveal melanomas (melanomas of the eye) are the most common primary intraocular malignancy. Melanomas of the eye can be divided into four predominant types: ciliary and choroidal melanomas, which account for most uveal melanomas, and iris and conjunctival melanomas, which are less common. This section will focus mainly on ciliary and choroidal melanomas, ie, uveal melanomas, and specific molecular characteristics of iris and conjunctival melanoma will be highlighted for comparison.
Uveal melanoma
MELANOMA STEM CELLS
The concept of cancer stem cells, or cancer-initiating cells, has gained considerable momentum in recent years. Although the identification of cancer stem cell-specific molecular aberrations is still in its infancy, the extent of the changes documented thus far and their potential implications for cancer therapy warrant a brief review.
Normal adult stem cells can be found in most somatic tissues, where they participate in renewal, repair, and maintenance of normal tissues. This essential
TARGETED MOLECULAR THERAPY
Despite decades of investigation, no systemic treatment that improves overall survival in most patients with unresectable metastatic melanoma has been developed. Occasional durable complete responses do occur in patients with metastatic disease who receive high-dose interleukin 2, biochemotherapy, and even chemotherapy alone; however, these occur in only 1% to 6% of patients, and no definitive tests exist to reliably predict these outcomes. During the past decade, only one agent has been
CONCLUSION
Our understanding of the molecular basis of melanoma has grown exponentially during the past decade. These scientific advances are likely to greatly affect the practice of medicine, including the diagnosis, prognosis, and treatment of melanoma. The enormous molecular complexity of melanoma and the realization that a clinical diagnosis of melanoma likely covers a spectrum of molecularly and mechanistically distinct entities highlight the need for better molecular disease classification and point
Glossary
- ABC
- adenosine triphosphate-binding casette
- ABCB5
- ABC subfamily B (MDR/TAP) member 5
- AIF
- apoptosis-inducing factor
- AIM1
- absent in melanoma 1
- AKT
- v-akt murine thymoma viral oncogene homolog
- APAF1
- apoptotic peptidase-activating factor 1
- ARAF
- v-raf murine sarcoma 3611 viral oncogene homolog
- BAD
- BCL2 antagonist of cell death
- BAK
- BCL2 homologous antagonist/killer
- BAX
- BCL2-associated X protein
- BCL2
- B cell chronic lymphocytic leukemia/lymphoma 2
- BID
- BH3-interacting domain death agonist
- BNIP3L
- BCL2/adenovirus E1B 19kDa
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Melanoma
2022, Genomic and Precision Medicine: Oncology, Third EditionNegative feedback regulation of ErbB4 tyrosine kinase activity by ERK-mediated non-canonical phosphorylation
2019, Biochemical and Biophysical Research CommunicationsOcular Tumors
2019, Abeloff’s Clinical OncologyHydroalcoholic extract of Spartium junceum L. flowers inhibits growth and melanogenesis in B16-F10 cells by inducing senescence
2018, PhytomedicineCitation Excerpt :Indeed, as suggested by Kim et al. (2014) and Liu-Smith and Meyskens (2016), both high levels of ROS and specific secondary metabolites seem to possess an antimelanogenic activity in melanoma and melanocytic cells. More in detail, they negatively target Mitf pathway, usually linked to cell life, differentiation and proliferation, which includes Tyrosinase (Tyr) and Tyrosine-related protein 1 (Tyrp1) enzymes (Markovic (2008)). To validate this theory, in treated B16-F10 cells, we measured the mRNA levels of Mitf, Tyr and Tyrp1 by qPCR (Fig. 3(A)) and the amount of Mitf protein by Western Blotting (Fig. 3(B) and (C)).
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Current Members of the Melanoma Study Group. Jacob B. Allred, BA; Panagiotis Z. Anastasiadis, PhD, MS; Keith H. Baratz, MD; Uldis Bite, MD; Elizabeth A. Bradley; Renee K. Bradshaw, MD; J. Douglas Cameron, MD; Ricky P. Clay, MD; Suzanne M. Connolly, MD; John A. Copland III, PhD; Edward T. Creagan, MD; Gary A. Croghan, MD, PhD; Mark Denis P. Davis, MD; Allan B. Dietz, PhD; John H. Donohue, MD; Lori A. Erickson, MD; David R. Farley, MD; Thomas J. Flotte, MD; Evanthia Galanis, MD; Yolanda I. (Nina) Garces, MD; James A. Garrity, MD; Dennis A. Gastineau, MD; Bobbie S. Gostout, MD; Clive S. Grant, MD; Jennifer L. Hand, MD; James N. Ingle, MD; Amer N. Kalaaji, MD; Jan L. Kasperbauer, MD; Judith S. Kaur, MD; Lisa A. Kottschade, RN; James Keeling, MD; Susan D. Laman, MD; Katherine K. Lim, MD; Noralane M. Lindor, MD; Charles L. Loprinzi, MD; Val Lowe, MD; Joseph Lustgarten, PhD; Leo J. Maguire, MD; William J. Maples, MD; Svetomir N. Markovic, MD, PhD; Colin A. McCannel, MD; Elizabeth S. McDonald, MD, PhD; Robert R. McWilliams, MD; Jane M. Milburn, MBA; Steven L. Moran, MD; Wendy K. Nevala, BS; Kerry D. Olsen, MD; Clark C. Otley, MD; Animesh Pardanani, MBBS, PhD; Galen Perdikis, MD; Mark R. Pittelkow, MD; Jeanette M. Pitts, MD; Barbara A. Pockaj, MD; Karl C. Podratz, MD, PhD; Jose S. Pulido, MD; Michael G. Rock, MD; Randall K. Roenigk, MD; John R Salassa, MD; Diva R. Salomao, MD; Steven E. Schild, MD; Aleksandar Sekulic, MD, PhD; Thomas C. Shives, MD; Franklin H. Sim, MD; John L. Snow, MD; C. Robert Stanhope, MD; W. P. Daniel Su, MD; Vera J. Suman, PhD; David L. Swanson, MD; Winston Tan, MD; Sarvam P. TerKonda, MD; Nho V. Tran, MD; Celine M. Vachon, PhD; Richard G. Vile, PhD; Stanimir Vuk-Pavlovic, PhD; James C. Waldorf, MD; Roger H. Weenig, MD; Ryan A. Wilcox, MD, PhD; Timothy O. Wilson, MD; Gregory A. Wiseman, MD