![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
REVIEW
1 Melanoma Program, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA; 2 Department of Dermatology, Harvard Medical School, Boston, Massachusetts 02115, USA; 3 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA; 4 The Broad Institute of Harvard and Massachussetts Institute of Technology, Cambridge, Massachusetts 02142, USA; 5 Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Children's Hospital of Boston, Boston, Massachusetts 02115, USA
Cell for cell, probably no human cancer is as aggressive as melanoma. It is among a handful of cancers whose dimensions are reported in millimeters. Tumor thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of metastatic melanoma carries with it an abysmal median survival of 6–9 mo. What features of this malignancy account for such aggressive behavior? Is it the migratory history of its cell of origin or the programmed adaptation of its differentiated progeny to environmental stress, particularly ultraviolet radiation? While the answers to these questions are far from complete, major strides have been made in our understanding of the cellular, molecular, and genetic underpinnings of melanoma. More importantly, these discoveries carry profound implications for the development of therapies focused directly at the molecular engines driving melanoma, suggesting that we may have reached the brink of an unprecedented opportunity to translate basic science into clinical advances. In this review, we attempt to summarize our current understanding of the genetics and biology of this disease, drawing from expanding genomic information and lessons from development and genetically engineered mouse models. In addition, we look forward toward how these new insights will impact on therapeutic options for metastatic melanoma in the near future.
[Keywords: Development; genetics; genomics; melanoma; therapeutics]
6 E-MAIL lynda_chin{at}dfci.harvard.edu; FAX (617) 582-8169.
7 E-MAIL david_fisher{at}dfci.harvard.edu; FAX (617) 632-2085.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1437206.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Reschke, D. Mihic-Probst, E. H. van der Horst, P. Knyazev, P. J. Wild, M. Hutterer, S. Meyer, R. Dummer, H. Moch, and A. Ullrich HER3 Is a Determinant for Poor Prognosis in Melanoma Clin. Cancer Res., August 15, 2008; 14(16): 5188 - 5197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Inoue-Narita, K. Hamada, T. Sasaki, S. Hatakeyama, S. Fujita, K. Kawahara, M. Sasaki, H. Kishimoto, S. Eguchi, I. Kojima, et al. Pten Deficiency in Melanocytes Results in Resistance to Hair Graying and Susceptibility to Carcinogen-Induced Melanomagenesis Cancer Res., July 15, 2008; 68(14): 5760 - 5768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Moore, D. L. Persons, J. A. Sosman, D. Bobadilla, V. Bedell, D. D. Smith, S. R. Wolman, R. J. Tuthill, J. Moon, V. K. Sondak, et al. Detection of Copy Number Alterations in Metastatic Melanoma by a DNA Fluorescence In situ Hybridization Probe Panel and Array Comparative Genomic Hybridization: A Southwest Oncology Group Study (S9431) Clin. Cancer Res., May 15, 2008; 14(10): 2927 - 2935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. S. Hodi, P. Friedlander, C. L. Corless, M. C. Heinrich, S. Mac Rae, A. Kruse, J. Jagannathan, A. D. Van den Abbeele, E. F. Velazquez, G. D. Demetri, et al. Major Response to Imatinib Mesylate in KIT-Mutated Melanoma J. Clin. Oncol., April 20, 2008; 26(12): 2046 - 2051. [Full Text] [PDF]
|
|
|
|
|
|
W. M. Lin, A. C. Baker, R. Beroukhim, W. Winckler, W. Feng, J. M. Marmion, E. Laine, H. Greulich, H. Tseng, C. Gates, et al. Modeling Genomic Diversity and Tumor Dependency in Malignant Melanoma Cancer Res., February 1, 2008; 68(3): 664 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Chetoui, K. Sylla, J.-V. Gagnon-Houde, C. Alcaide-Loridan, D. Charron, R. Al-Daccak, and F. Aoudjit Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis Mol. Cancer Res., January 1, 2008; 6(1): 42 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-H. Liao, S.-M. Hsu, and P.-H. Huang ARMS Depletion Facilitates UV Irradiation Induced Apoptotic Cell Death in Melanoma Cancer Res., December 15, 2007; 67(24): 11547 - 11556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Abbas, A. Bhoumik, R. Dahl, S. Vasile, S. Krajewski, N. D.P. Cosford, and Z. A. Ronai Preclinical Studies of Celastrol and Acetyl Isogambogic Acid in Melanoma Clin. Cancer Res., November 15, 2007; 13(22): 6769 - 6778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chandramouli, J. Shi, Y. Feng, H. Holubec, R. M.Shanas, A. K. Bhattacharyya, W. Zheng, and M. A. Nelson Haploinsufficiency of the cdc2l gene contributes to skin cancer development in mice Carcinogenesis, September 1, 2007; 28(9): 2028 - 2035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ha, T. Ichikawa, M. Anver, R. Dickins, S. Lowe, N. E. Sharpless, P. Krimpenfort, R. A. DePinho, D. C. Bennett, E. V. Sviderskaya, et al. ARF functions as a melanoma tumor suppressor by inducing p53-independent senescence PNAS, June 26, 2007; 104(26): 10968 - 10973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Stecca, C. Mas, V. Clement, M. Zbinden, R. Correa, V. Piguet, F. Beermann, and A. Ruiz i Altaba Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways PNAS, April 3, 2007; 104(14): 5895 - 5900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mohapatra, D. Coppola, A. I. Riker, and W. J. Pledger Roscovitine Inhibits Differentiation and Invasion in a Three-Dimensional Skin Reconstruction Model of Metastatic Melanoma Mol. Cancer Res., February 1, 2007; 5(2): 145 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Verhaegen, J. A. Bauer, C. Martin de la Vega, G. Wang, K. G. Wolter, J. C. Brenner, Z. Nikolovska-Coleska, A. Bengtson, R. Nair, J. T. Elder, et al. A Novel BH3 Mimetic Reveals a Mitogen-Activated Protein Kinase-Dependent Mechanism of Melanoma Cell Death Controlled by p53 and Reactive Oxygen Species Cancer Res., December 1, 2006; 66(23): 11348 - 11359. [Abstract] [Full Text] [PDF]
|
|
