Melanoma: Translational Research and Emerging Therapies PDF

Preface

There are an estimated 160,000 patients newly diagnosed with melanoma annually worldwide. The lifetime risk of developing this disease in the United States is estimated at 1 in 49 for men and 1 in 73 for women. While the majority of patients diagnosed in early stages have a good outlook for cure, the prognosis of patients diagnosed after the disease has spread to distant sites remains grim.

The treatment of melanoma is truly multidisciplinary and involves input from diverse specialties including dermatology, surgical, medical and radiation oncology, nursing, and supportive care. The crucial and often-forgotten ‘‘unsung heroes'' in the battle against this disease are the laboratory scientists who silently carry on the crusade to find newer therapies for clinicians to offer their patients. In this regard, this book attempts to bring together the clinician and the researcher in a format that addresses several important aspects of melanoma research and therapy, spanning the spectrum from prevention and etiology of the disease to the genetic makeup of advanced metastatic melanoma. Hence the name ‘‘Translational and Emerging Therapies.''

Dr. Berwick addresses the controversies and difficulty in understanding the role of ultraviolet radiation in the pathogenesis of melanoma, including the potential role of tanning parlors in melanoma etiology, in chapter 1.

No translational text on melanoma would be complete without a discussion on molecular pathways, and in the next chapter, Dr. Fecher provides a comprehensive overview, with particular focus on signal transduction pathways as potential therapeutic targets.

Pediatric melanoma is fortunately a relative rare event, but is increasing in incidence and attracting greater attention. Diagnosis of melanomas in childhood poses inherent challenges, and several areas of controversy exist in terms of classifying melanocytic lesions in childhood. Drs. Celebi and Messina tackle the difficult topic of Spitzoid melanomas in chapter 3.

Drs. Daud, Sondak, and Weeraratna provide a comprehensive overview of melanoma genomics and implications for therapy. This is a burgeoning field and is likely to be the platform on which many new and exciting therapeutic targets will be identified.

Chemoprevention of melanoma is an attractive concept and is being explored in diseases such as breast cancer and familial adenomatous polyposis. Dr. Demierre provides an up-to-date review of the current status of chemoprevention strategies in melanoma, with emphasis on targeting Ras signaling. The molecular pathway in melanoma that has received the most therapeutic attention is the BRAF pathway downstream of Ras. Indeed, several agents targeting BRAF either singly or in combination with chemotherapy are in clinical trials for advanced melanoma patients. Drs. Smalley and Flaherty outline the rationale for the exploitation of this pathway as a paradigm for melanoma therapy.

The role that stem cells play in cancer development, progression and metastasis is receiving increasing attention. Drs. Smalley, Desai and Herlyn tackle this important topic in chapter 7, making the argument that therapies for melanoma are not likely to be successful unless they affect and modify the stem cell population.

The importance of skin pigmentation and the role of micropthalmiaassociated transcription factor is an exciting area of current research with potentially druggable targets. Drs. Haq and Fisher discuss the current state-of-the-art in this area.

Recombinant interferon alfa is an agent that is widely used in melanoma and is approved for use in the adjuvant setting. Although clinically effective, the mechanisms by which this agent exerts its therapeutic effect are still unclear. The chapter by Drs. Lesinski and Carson provides an overview of the topic and places into context what is known about mechanisms of interferon activity. Drs. Gogas and Kirkwood address a very important area of research with interferon: How can we target this toxic agent to individuals most likely to benefit? The exciting findings as related to autoimmunity and their potential impact on interferon effectiveness are discussed.

Clinical data with the use of vaccines in melanoma has been disappointing despite apparent potential in the laboratory. Dr. Vohra and colleagues provide a timely review of this topic, with emphasis on potential approaches to optimizing vaccine therapy and selecting appropriate patients for future clinical trials. Finally, Drs. Tsai and Chang provide an update on the role of adoptive immunotherapy, an approach that has been shown to be clinically effective in selective patients as far back as the 1960s.

The difficult issues surrounding procurement of melanoma tumor tissue for research purposes in the face of providing adequate tissue for diagnosis are elegantly addressed by Dr. Hoover and colleagues from the Moffitt Cancer Center, where a very successful melanoma tissue procurement program is in place. The fact that most melanomas are diagnosed in the primary physician's or dermatologist's office, removed entirely and therefore not often available for academic study, makes this a particularly challenging problem.

Finally, we have attempted to provide a glossary of technical terms for easy reference as they appear in the text. This should facilitate the reader with quick definitions of sometimes confusing terminology.

The explosion of revolutionary basic science methodologies and the ability to probe the tumor down to the molecular level have enabled us to understand disease at a basic level and potentially devise therapeutic choices based on real information. It is only a matter of time before the elusive breakthrough is here.