Cutaneous Melanoma—A Long Road from Experimental Models to Clinical Outcome: A Review

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Abstract

Cutaneous melanoma is a complex disorder characterized by an elevated degree of heterogeneity, features that place it among the most aggressive types of cancer. Although significant progress was recorded in both the understanding of melanoma biology and genetics, and in therapeutic approaches, this malignancy still represents a major problem worldwide due to its high incidence and the lack of a curative treatment for advanced stages. This review offers a survey of the most recent information available regarding the melanoma epidemiology, etiology, and genetic profile. Also discussed was the topic of cutaneous melanoma murine models outlining the role of these models in understanding the molecular pathways involved in melanoma initiation, progression, and metastasis.

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Final version of 2009 AJCC melanoma staging and classification.

Charles M. Balch, Jeffrey Gershenwald, Seng-jaw Soong … (2010)

To revise the staging system for cutaneous melanoma on the basis of data from an expanded American Joint Committee on Cancer (AJCC) Melanoma Staging Database. The melanoma staging recommendations were made on the basis of a multivariate analysis of 30,946 patients with stages I, II, and III melanoma and 7,972 patients with stage IV melanoma to revise and clarify TNM classifications and stage grouping criteria. Findings and new definitions include the following: (1) in patients with localized melanoma, tumor thickness, mitotic rate (histologically defined as mitoses/mm(2)), and ulceration were the most dominant prognostic factors. (2) Mitotic rate replaces level of invasion as a primary criterion for defining T1b melanomas. (3) Among the 3,307 patients with regional metastases, components that defined the N category were the number of metastatic nodes, tumor burden, and ulceration of the primary melanoma. (4) For staging purposes, all patients with microscopic nodal metastases, regardless of extent of tumor burden, are classified as stage III. Micrometastases detected by immunohistochemistry are specifically included. (5) On the basis of a multivariate analysis of patients with distant metastases, the two dominant components in defining the M category continue to be the site of distant metastases (nonvisceral v lung v all other visceral metastatic sites) and an elevated serum lactate dehydrogenase level. Using an evidence-based approach, revisions to the AJCC melanoma staging system have been made that reflect our improved understanding of this disease. These revisions will be formally incorporated into the seventh edition (2009) of the AJCC Cancer Staging Manual and implemented by early 2010.

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Melanoma.

Arlo J. Miller, Martin C. Mihm (2006)

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L-tyrosine and L-dihydroxyphenylalanine as hormone-like regulators of melanocyte functions.

Andrzej T. Slominski, Michal Zmijewski, John Pawelek (2012)

There is evidence that L-tyrosine and L-dihydroxyphenylalanine (L-DOPA), besides serving as substrates and intermediates of melanogenesis, are also bioregulatory agents acting not only as inducers and positive regulators of melanogenesis but also as regulators of other cellular functions. These can be mediated through action on specific receptors or through non-receptor-mediated mechanisms. The substrate induced (L-tyrosine and/or L-DOPA) melanogenic pathway would autoregulate itself as well as regulate the melanocyte functions through the activity of its structural or regulatory proteins and through intermediates of melanogenesis and melanin itself. Dissection of regulatory and autoregulatory elements of this process may elucidate how substrate-induced autoregulatory pathways have evolved from prokaryotic or simple eukaryotic organisms to complex systems in vertebrates. This could substantiate an older theory proposing that receptors for amino acid-derived hormones arose from the receptors for those amino acids, and that nuclear receptors evolved from primitive intracellular receptors binding nutritional factors or metabolic intermediates. © 2011 John Wiley & Sons A/S.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 24 May 2018

Publication date Collection: June 2018

Volume: 19

Issue: 6

Electronic Location Identifier: 1566

Affiliations

[1 ]Department of Toxicology, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 300041 Timişoara, Romania; dorinacoricovac@ 123456umft.ro (D.C.); cadehelean@ 123456umft.ro (C.D.); alina.moaca@ 123456umft.ro (E.-A.M.); iuliapinzaru@ 123456umft.ro (I.P.)

[2 ]Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, 300041 Timişoara, Romania; drbratu@ 123456brol.ro (T.B.); ovidiuboruga@ 123456yahoo.com (O.B.)

[3 ]Department of Obstetrics-Gynecology and Neonatology, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timișoara, Romania

Author notes

[* ]Correspondence: navolan@ 123456yahoo.com ; Tel.: +40-722-960-911

[†]

These authors contributed equally to this work.

Author information

Dorina Coricovac https://orcid.org/0000-0002-5760-8872

Elena-Alina Moaca https://orcid.org/0000-0002-2631-7028

Iulia Pinzaru https://orcid.org/0000-0003-2295-1926

Article

Publisher ID: ijms-19-01566

DOI: 10.3390/ijms19061566

PMC ID: 6032347

PubMed ID: 29795011

SO-VID: 02827949-7647-4137-9910-abfc2c8140d4

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Cutaneous Melanoma—A Long Road from Experimental Models to Clinical Outcome: A Review

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Abstract

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Animal models of intrauterine growth restriction (IUGR)

Most cited references 94

Final version of 2009 AJCC melanoma staging and classification.

Melanoma.

L-tyrosine and L-dihydroxyphenylalanine as hormone-like regulators of melanocyte functions.

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