Virtual issue on Melanoma

Most recent reviews and articles on melanoma [2008] [2007] [2006] [2005]

Melanoma – a look down the road ahead

By Ze’ev Ronai, PhD, Burnham Institute for Medical Research, La Jolla, USA www.ronailab.net

Malignant melanoma is one of the most highly invasive and metastatic tumors. Correspondingly, the primary clinical barriers to effective melanoma treatment are the high propensity for tumors to metastasize and the strong resistance of tumors to available treatments.

A significant advance in understanding melanoma biology was made over recent years when genetic changes along the MAPK signaling pathway (B-Raf and N-Ras mutations) were identified. Identification of these types of mutations in many melanoma tumors has significantly increased our understanding of genetic changes underlying melanoma. Yet, it is critical to note that identical genetic changes do not always underlie different melanoma subtypes. For example, mutations seen in melanomas associated with sun exposure differ from those seen in other subtypes, and some melanoma subtypes exhibit mutations in signaling pathways other than MAPK kinase. For example, c-Kit mutations were found in about 30% of mucosal, acral and other melanomas developing on chronically sun-exposed skin, conditions in which mutations in MAPK pathway components were not seen. Thus, while we have greatly advanced our understanding melanoma as a cancer marked by deregulation of well-defined signaling pathways, it is now clear that changes in multiple pathways exist among melanoma subtypes. Understanding these differences will dictate how selective therapies are developed and applied.

Adding to the complexity is the growing recognition that pathways are re-wired in melanoma. In tumors, MAPK-related pathways intersect with and influence regulatory pathways not thought to be linked in normal cells. Thus, the molecular analysis of changes in melanoma will require extensive dissection of multiple pathways influenced by deregulated genes. For example, further understanding of mechanisms underlying deregulated AKT signaling in melanoma awaits characterization.

Equally important is the growing realization that central to the etiology of melanoma is a small but potent population of melanoma initiating (stem?) cells. This exciting topic is receiving growing attention and should provide important insight into the handful of cells capable of initiating a tumor. Although currently only a few groups are dedicating their efforts to this exciting observation, an emerging theme in cancer research is that melanoma initiating cells may be as complex as melanoma tumors are.

Understanding tumor microenvironment has been and will remain critical to our understanding of melanoma progression, given that a hallmark of melanoma is its metastatic potential. The development of mouse models and better technologies to study tumor microenvironment (from 3D cultures to lymph-angiogenesis) provides tools necessary for identifying mechanisms underlying melanoma metastasis and finding selective means to halt it, as well as models to assess possible therapeutic approaches.

The growing number of selective markers used to detect melanoma tumors and follow metastatic lesions, combined with improved imaging technologies, generate optimism that we will devise better diagnostics and more efficient treatment strategies.

Together with these exciting developments in basic research come extensive efforts to develop drugs specifically targeting a given signaling pathway. Some newly developed drugs targeting B-Raf mutations are presently in clinical trials; other drugs, such as those available to treat melanomas harboring c-Kit mutations, are being also evaluated. With high expectations for the success of selective treatment regimens, we also recognize that targeting a single regulatory component may not be sufficient for melanoma therapy. Thus we must identify and better characterize other targets associated with deregulated pathways in melanoma in order to treat this tumor type efficiently and selectively.

Recent Articles Published on Melanoma

2008

The reactive oxygen-driven tumor: relevance to melanoma
Levi Fried, Jack L. Arbiser
April 2008

Transforming growth factor-β in cutaneous melanoma
Delphine Javelaud, Vasileia-Ismini Alexaki, Alain Mauviel
April 2008

Melanoma initiating cells - easy as ABC?
Anindita Bhoumik, Ze’ev Ronai
April 2008

Involvement of FKHRL1 in melanoma cell survival and death
C. Hilmi, L. Larribere, M. Deckert, S. Rocchi, S. Giuliano, K. Bille, J.P. Ortonne, R. Ballotti, C. Bertolotto
April 2008

Identification of differentially expressed genes in spontaneously regressing melanoma using the MeLiM Swine Model
F. Rambow, O. Malek, C. Geffrotin, J.-J. Leplat, S. Bouet, G. Piton, K. Hugot, C. Bevilacqua, V. Horak, S. Vincent-Naulleau
April 2008

How to make a melanoma: what do we know of the primary clonal events?
Dorothy C. Bennett
February 2008

Cancer stem cells and human malignant melanoma
Tobias Schatton and Markus H Frank
February 2008

2007

The many faces of Notch signaling in skin-derived cells
Chelsea C. Pinnix and Meenhard Herlyn
Pages 458–465
December 2007

DNA microarray analyses of melanoma gene expression: a decade in the mines
Keith S. Hoek
Pages 466–484
December 2007

Cutaneous melanoma in genetically modified animals
Lionel Larue and Friedrich Beermann
Pages 485–497
December 2007

ATF2 on the double – activating transcription factor and DNA damage response protein
Anindita Bhoumik, Pablo Lopez-Bergami and Ze’ev Ronai
Pages 498–506
December 2007

Melanoma senescence: HDAC1 in focus
Colin R. Goding
Pages 336-338
October 2007

Potent p53-independent tumor suppressor activity of ARF in melanoma-genesis
Hans R. Widlund, David E. Fisher
Pages 339–340
October 2007

The HOG-GLI face of melanoma
Menashe Bar-Eli
Pages 341-342
October 2007

Detection of melanoma cells in sentinel lymph nodes by PCR is not yet ready for prime time
Paul B. Chapman
Pages 343–344
October 2007

Wnt5a and PKC, a deadly partnership involved in melanoma invasion
Estela E. Medrano
pages 258–259
August 2007

Melanoma invasion – current knowledge and future directions
Cedric Gaggioli and Erik Sahai
June 2007

Confirmation of a BRAF mutation-associated gene expression signature in melanoma
Peter Johansson, Sandra Pavey and Nicholas Hayward
June 2007

Molecular markers of circulating melanoma cells
Sandra Medic, Robert L. Pearce, Peter J. Heenan and Mel Ziman
pages 80–91
April 2007

Epigenetic events in malignant melanoma
Tanja Rothhammer and Anja-Katrin Bosserhoff
pages 92–111
April 2007

Loss of maspin expression contributes to a more invasive potential in malignant melanoma
Alexandra E. Denk, Marcus Bettstetter, Peter J. Wild, Keith Hoek, Frauke Bataille, Wolfgang Dietmaier and Anja K. Bosserhoff
pages 112–119
April 2007

2006

Bioimmunotherapy for melanoma using fully human antibodies targeting MCAM/MUC18 and IL-8
Vladislava O. Melnikova, Menashe Bar-Eli
October 2006

Pocket protein function in melanocyte homeostasis and neoplasia
Ian D. Tonks, Nicholas K. Hayward, Graham F. Kay
August 2006

Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature
Keith S. Hoek, Natalie C. Schlegel, Patricia Brafford, Antje Sucker, Selma Ugurel, Rajiv Kumar, Barbara L. Weber, Katherine L. Nathanson, David J. Phillips, Meenhard Herlyn, Dirk Schadendorf, Reinhard Dummer
August 2006

NF-κB activation in melanoma
Yukiko Ueda, Ann Richmond
April 2006

Apaf-1 expression in human cutaneous melanoma progression and in pigmented nevi
Katarzyna Niedojad?o, Karolina ?abeœdzka, Ewelina ?ada, Agnieszka Milewska, Barbara W. Chwirot
Katarzyna Niedojadlo, Karolina Labedzka, Ewelina Lada, Agnieszka Milewska, Barbara W. Chwirot
February 2006

Glutamate receptors on human melanocytes regulate the expression of MiTF
M. J. Hoogduijn, I. S. Hitchcock, N. P. M. Smit, J. M. Gillbro, K. U. Schallreuter, P. G. Genever
February 2006

2005

Melanoma inhibitory activity (MIA): an important molecule in melanoma development and progression
Anja-Katrin Bosserhoff
December 2005

Adhesion, migration and communication in melanocytes and melanoma
Nikolas K. Haass, Keiran S. M. Smalley, Ling Li, Meenhard Herlyn
June 2005

Histone deacetylase inhibitors and malignant melanoma
Glen M. Boyle, Adam C. Martyn, Peter G. Parsons
June 2005

Original articles
Melanoma cell lines are susceptible to histone deacetylase inhibitor TSA provoked cell cycle arrest and apoptosis
Karita Peltonen, Taija M. Kiviharju, Päivi M. Järvinen, Runar Ra, Marikki Laiho
June 2005

Inhibition of melanoma inhibitory activity (MIA) expression in melanoma cells leads to molecular and phenotypic changes
Jutta Tatzel, Ina Poser, Josef Schroeder, Anja K Bosserhoff
April 2005

Principal expression of two mRNA isoforms (ABCB 5 and ABCB 5 ) of the ATP-binding cassette transporter gene ABCB 5 in melanoma cells and melanocytes
Kevin G. Chen, Gergely Szakács, Jean-Philippe Annereau, Francois Rouzaud, Xing-Jie Liang, Julio C. Valencia, Chandrasekharam N. Nagineni, John J. Hooks, Vincent J. Hearing, Michael M. Gottesman
April 2005

Decreased expression of Apaf-1 with progression of melanoma
Rita Mustika, Arief Budiyanto, Chikako Nishigori, Masamitsu Ichihashi, Masato Ueda
February 2005