RECENT ADVANCES IN THE BIOLOGY, THERAPY AND MANAGEMENT OF MELANOMA Edited by Lester M Davids Recent Advances in the Biology, Therapy and Management of Melanoma http://dx.doi.org/10.5772/46052 Edited by Lester M Davids Contributors Pu Wang, Peipei Guan, Sadako Yamagata, Tatsuya Yamagata, Shawn M Swavey, John D'Orazio, James Lagrew, Amanda Marsch, Stuart Jarrett, Laura Cleary, Norma E Herrera, Jianli Dong, Gengming Huang, Rasheen Imtiaz, Fangling Xu, Randy Burd, Erin Mendoza, Nicholas Panayi, Elliot Breshears, Paola Savoia, Paolo Fava, Pietro Quaglino, Maria Grazia Bernengo, Jung-Feng Hsieh, Wen-Tai Li, Hsiang-Wen Tseng, Isabel Pires, Justina Prada, Felisbina Luisa Queiroga, Joana Almeida Gomes, Dinora Pereira, Miriam Jasiulionis, Fabiana Melo, Fernanda Molognoni, Bryan E Strauss, Eugenia Costanzi-Strauss, Małgorzata Latocha, Aleksandra Zielińska, Magdalena Jurzak, Dariusz Kuśmierz, Jiri Vachtenheim, Brian Wall, Tania Creczynski-Pasa Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2013 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work Any republication, referencing or personal use of the work must explicitly identify the original source Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher No responsibility is accepted for the accuracy of information contained in the published chapters The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book Publishing Process Manager Ana Pantar Technical Editor InTech DTP team Cover InTech Design team First published February, 2013 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Recent Advances in the Biology, Therapy and Management of Melanoma, Edited by Lester M Davids p cm ISBN 978-953-51-0976-1 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface VII Section Melanoma Epidemiology Chapter Melanoma — Epidemiology, Genetics and Risk Factors John A D’Orazio, Stuart Jarrett, Amanda Marsch, James Lagrew and Laura Cleary Section Molecular Mechanisms 37 Chapter Aberrant Death Pathways in Melanoma 39 Nicholas D Panayi, Erin E Mendoza, Elliot S Breshears and Randy Burd Chapter Interaction Between the Immune System and Melanoma 53 Norma E Herrera-Gonzalez Chapter MITF: A Critical Transcription Factor in Melanoma Transcriptional Regulatory Network 71 Jiri Vachtenheim and Lubica Ondrušová Chapter The Role of Oxidative Stress in Melanoma Development, Progression and Treatment 83 Fabiana Henriques Machado de Melo, Fernanda Molognoni and Miriam Galvonas Jasiulionis Chapter Expression of Matrix Metalloproteinases and Theirs Tissue Inhibitors in Fibroblast Cultures and Colo-829 and SH-4 Melanoma Cultures After Photodynamic Therapy 111 Aleksandra Zielińska, Małgorzata Latocha, Magdalena Jurzak and Dariusz Kuśmierz VI Contents Chapter MMP-2 and MMP-9 Expression in Canine Cutaneous Melanocytic Tumours: Evidence of a Relationship with Tumoural Malignancy 133 Isabel Pires, Joana Gomes, Justina Prada, Dinora Pereira and Felisbina L Queiroga Chapter Glutamate Signaling in Human Cancers 163 Brian A Wall, Seung-Shick Shin and Suzie Chen Section Therapeutics 187 Chapter Current Therapies and New Pharmacologic Targets for Metastatic Melanoma 189 Claudriana Locatelli, Fabíola Branco Filippin-Monteiro and Tânia Beatriz Creczynski-Pasa Chapter 10 Targeted Agents for the Treatment of Melanoma: An Overview 231 Hsiang-Wen Tseng, Wen-Tai Li⁺ and Jung-Feng Hsieh⁺ Chapter 11 Porphyrin and Phthalocyanine Photosensitizers as PDT Agents: A New Modality for the Treatment of Melanoma 253 Shawn Swavey and Matthew Tran Chapter 12 Gene Therapy for Melanoma: Progress and Perspectives 283 Bryan E Strauss and Eugenia Costanzi-Strauss Chapter 13 The Potential Importance of K Type Human Endogenous Retroviral Elements in Melanoma Biology 319 Jianli Dong, Gengming Huang, Rasheen Imtiaz and Fangling Xu Chapter 14 Emerging GM3 Regulated Biomarkers in Malignant Melanoma 339 Pu Wang*, Peipei Guan*, Su Xu, Zhanyou Wang, Sadako Yamagata and Tatsuya Yamagata Chapter 15 After Surgery: Follow-Up Guidelines of Melanoma Patients 361 Paolo Fava, Pietro Quaglino, Maria Grazia Bernengo and Paola Savoia Preface The book Recent Advances in the Biology, Therapy and Management of Melanoma brings the latest, up-to-date information regarding the biological mechanisms underlying melano‐ ma epidemiology, molecular mechanisms and the therapeutic options that are employed in combating this dreaded disease The first section covers the genetics of melanoma develop‐ ment with associated risk factors Understanding the underlying molecular mechanisms of melanomagenesis, the biomarkers, and the proteins that contribute to melanoma, all lead to illuminating potential targets in the fight against this disease This section is comprehensive‐ ly reviewed and is essential to be interweaved and translated with the final section which culminates in current treatment options and clinically relevant regimes The novelty of new treatment options are further highlighted in this section This book is intended to be a reference book for both the scientific and clinical communities It is not often easy to interweave these two disciplines but this book brings both of these together in an easy, readable way The fact that there is so much ongoing scientific and clini‐ cal research in the field of melanoma is an indicator of the importance and relevance attach‐ ed to understanding the human melanocyte and the factors that cause it to go awry This fundamental scientific understanding has to then be translated to the clinic in order for us to make significant strides in eradicating this dreaded disease It is hoped that scientists, clinicians, students and residents find this book useful in their studies on melanoma and that it not only expands their perspectives and views on the field, but challenges them to forge ahead towards discovering the ultimate cure Lester M Davids Redox Laboratory, Department of Human Biology, Faculty of Health Sciences University of Cape Town, South Africa Section Melanoma Epidemiology 362 Recent Advances in the Biology, Therapy and Management of Melanoma rate was found for melanomas located on the head-neck, back, anterior trunk, upper limb and thigh-leg; conversely, a primary melanoma located to the foot was associated to a statistically significant higher relapse rate with respect to all the other sites (Quaglino et al 2007) As regard the first site of metastatic spreading, patients with a lower limb primary melanoma showed more frequently loco-regional metastases, whereas distant spreading was mainly observed in patients with melanoma located in the trunk (Savoia et al 2009) More in details, lower limb location showed a low incidence of visceral metastases as first site of relapse, irrespectively of the AJCC stage, compared to all other body sites (Quaglino et al 2007) Clinical Staging Pathological Staging Tis N0 M0 Tis N0 M0 IA T1a N0 M0 IA T1a N0 M0 IB IB IIB N0 M0 N0 M0 T2b N0 M0 T3a IIA T1b T2a N0 M0 T3b N0 M0 IIB N0 M0 N0 M0 T2b N0 M0 T3a IIA T1b T2a N0 M0 T3b N0 M0 T4a N0 M0 T4a N0 M0 IIC T4b N0 M0 IIC T4b N0 M0 III any T N 1-3 M0 IIIA T1-T4a N1a/2a M0 IIIB T1-T4b N1a/2a M0 T1-T4a N1b/2b M0 T1-T4a/b IV any T any N M1 IV N2c M0 T1-T4b N1b/2b/2c M0 any T IIIC N3 M0 any T any N M1 Table Clinical and pathological staging, AJCC 2009 The majority of guidelines encourage frequent clinical and radiological examination during the first years from the diagnosis, due to the fact that almost 90% of all metastases occur during this period (Dummer et al 2011) However, it has been demonstrated that the time course of first relapse depend to the AJCC stage: the progressive decrease of relapse trend and the subsequent plateau is reached earlier in stage IA (after the second year) and later in stage IIB/IIC (from 5th to 8th year); moreover, distant relapses as first site of recurrences showed a low (