Editorial...
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Hindawi Publishing Corporation Dermatology Research and Practice Volume 2010, Article ID 798324, 2 pages doi:10.1155/2010/798324 Editorial From Melanocyte to Malignant Metastatic Melanoma Prashiela Manga, 1 Keith S. Hoek, 2 Lester M. Davids, 3 and Sancy A. Leachman 4 1 The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, 522 First Avenue, New York, NY 10016, USA 2 Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland 3 Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa 4 Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA Correspondence should be addressed to Prashiela Manga, [email protected] Received 10 August 2010; Accepted 10 August 2010 Copyright © 2010 Prashiela Manga et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Incidence of melanoma, the deadliest form of skin cancer, continues to increase among older adults and young women worldwide despite significant efforts to raise awareness and inform the public about risk factors such as sun exposure, use of tanning salon, and the need to monitor skin for potential neoplastic lesions. Whether this increase is due to an actual rise in the number of individuals that develop the disease or due to an increase in classification of lesions as melanoma remains contentious; however it is indisputable that lim- ited progress has been made in improving treatment of malignant melanoma or mortality rates. While new targeted agents against BRAF and immunotherapies directed against CTLA4 are showing great promise in clinical trials, FDA- approved therapies for melanoma remain largely ineffective, highlighting the need to better understand the mechanisms underlying disease initiation and progression. Melanoma results from malignant transformation of melanocytes. The most frequent site of transformation is in the skin where melanocytes produce the pigment melanin that confers skin color and protects against sun-induced damage. Multiple factors contribute to melanoma risk, including genetic predisposition and environmental risk factors such as sun exposure. In this special issue, we present six papers that review some of the crucial issues currently being investigated in the melanoma field. B. Bandarchi et al. provide a broad review of malig- nant melanoma, from epidemiology and risk factors to classification and clinical features, highlighting some of the genes that play a role in disease progression. Furthermore they review treatment options and discuss the 2009 Amer- ican Joint Committee on Cancer Melanoma Staging and Classification. J. A. H. Lee explores the relationship between incidence rates for in situ and invasive melanoma, proposing that the trends may in fact provide clues to the mechanisms that underlie development and progression of melanoma. R. Ria et al. review the events and consequences of increasing vascularization during tumorigenesis and sum- marize the most relevant cytokines involved. They also detail the roles of melanoma-produced factors involved in interacting with or modifying the extracellular environment in favour of neovascularizing processes. Finally, these authors discuss recent efforts to therapeutically target tumor vas- cularization in patients using a variety of small molecule inhibitors, concluding that there remains much room for improvement. A group led by Annelies de Klein (T. van den Bosch et al.) compare cutaneous and uveal melanomas and find that while diagnosis and therapy options are similar, there are telling differences in the biology of these malignances. For example, cutaneous melanomas may metastasize to a variety of organs in the body while most uveal melanomas metastasize to the liver; the authors point out that this difference is likely due to the absence of lymphatic vessels associated with the eye. Perhaps most interesting are the cytogenetic differences discussed, the most prominent example being that monosomy 3 is a common feature of uveal melanomas which is rarer in the cutaneous disease.
Transcript of Editorial...
Hindawi Publishing CorporationDermatology Research and PracticeVolume 2010, Article ID 798324, 2 pagesdoi:10.1155/2010/798324
Editorial
From Melanocyte to Malignant Metastatic Melanoma
Prashiela Manga,1 Keith S. Hoek,2 Lester M. Davids,3 and Sancy A. Leachman4
1 The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, 522 First Avenue,New York, NY 10016, USA
2 Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland3 Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa4 Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
Correspondence should be addressed to Prashiela Manga, [email protected]
Received 10 August 2010; Accepted 10 August 2010
Copyright © 2010 Prashiela Manga et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.
Incidence of melanoma, the deadliest form of skin cancer,continues to increase among older adults and young womenworldwide despite significant efforts to raise awareness andinform the public about risk factors such as sun exposure, useof tanning salon, and the need to monitor skin for potentialneoplastic lesions. Whether this increase is due to an actualrise in the number of individuals that develop the disease ordue to an increase in classification of lesions as melanomaremains contentious; however it is indisputable that lim-ited progress has been made in improving treatment ofmalignant melanoma or mortality rates. While new targetedagents against BRAF and immunotherapies directed againstCTLA4 are showing great promise in clinical trials, FDA-approved therapies for melanoma remain largely ineffective,highlighting the need to better understand the mechanismsunderlying disease initiation and progression. Melanomaresults from malignant transformation of melanocytes. Themost frequent site of transformation is in the skin wheremelanocytes produce the pigment melanin that confers skincolor and protects against sun-induced damage. Multiplefactors contribute to melanoma risk, including geneticpredisposition and environmental risk factors such as sunexposure. In this special issue, we present six papers thatreview some of the crucial issues currently being investigatedin the melanoma field.
B. Bandarchi et al. provide a broad review of malig-nant melanoma, from epidemiology and risk factors toclassification and clinical features, highlighting some of thegenes that play a role in disease progression. Furthermore
they review treatment options and discuss the 2009 Amer-ican Joint Committee on Cancer Melanoma Staging andClassification.
J. A. H. Lee explores the relationship between incidencerates for in situ and invasive melanoma, proposing that thetrends may in fact provide clues to the mechanisms thatunderlie development and progression of melanoma.
R. Ria et al. review the events and consequences ofincreasing vascularization during tumorigenesis and sum-marize the most relevant cytokines involved. They alsodetail the roles of melanoma-produced factors involved ininteracting with or modifying the extracellular environmentin favour of neovascularizing processes. Finally, these authorsdiscuss recent efforts to therapeutically target tumor vas-cularization in patients using a variety of small moleculeinhibitors, concluding that there remains much room forimprovement.
A group led by Annelies de Klein (T. van den Bosch et al.)compare cutaneous and uveal melanomas and find that whilediagnosis and therapy options are similar, there are tellingdifferences in the biology of these malignances. For example,cutaneous melanomas may metastasize to a variety of organsin the body while most uveal melanomas metastasize tothe liver; the authors point out that this difference islikely due to the absence of lymphatic vessels associatedwith the eye. Perhaps most interesting are the cytogeneticdifferences discussed, the most prominent example beingthat monosomy 3 is a common feature of uveal melanomaswhich is rarer in the cutaneous disease.
2 Dermatology Research and Practice
J. F. G. Cohen-Solal and coworkers review melanoma’scapacity for immune escape, reminding us of extensivestudies conducted by themselves and other groups whichshow that expression of Fc-gamma receptor decoys serves toprevent immune effector cells from recognizing melanomacells and providing answers as to how melanoma has sofar avoided targeted immunotherapy. They close with thehopeful note that it may be possible to design Fc fragmentswith reduced affinity for decoys and higher affinity forimmune-functional receptors.
The Italian group of M. Sanzo et al. review chronic stressas a possible cofactor in the progression of melanoma. Astreatment of this dreaded disease continues to be ineffective,this hypothesis is worth exploring. They suggest in theirpaper that despite understanding biological mechanismsunderlying local and distant metastases, the effect of stressmediator molecules such as catecholamines may increaseprogression. These findings point to the complexity of can-cers in that chronic stress including both psychological andenvironmental factors may influence biological pathways.Finally, these authors suggest that intervention targetingthese catecholinergic hormones in addition to psychologicaland social support may represent a valid approach in thetreatment of advanced melanoma.
Prashiela MangaKeith S. Hoek
Lester M. DavidsSancy A. Leachman
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