Advances in melanoma:
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
Philadelphia, PA
Saunders
2009
|
| Schriftenreihe: | Hematology, oncology clinics of North America
23,3 |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XIV S., S. 383 - 631 Ill., graph. Darst. |
| ISBN: | 9781437704884 1437704883 |
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Datensatz im Suchindex
| _version_ | 1804139257153978368 |
|---|---|
| adam_text | Titel: Advances in melanoma
Autor: Fisher, David E.
Jahr: 2009
Advances in Melanoma
Contents
Preface xiii
David E. Fisher
Melanoma Epidemiology 383
Margaret A. Tucker
Melanoma is a complex, heterogeneous cancer that continues to increase
in incidence. Multiple studies have consistently identified major host and
environmental risk factors for melanoma. Nevi, particularly dysplastic
nevi, confer much higher risks than most pigmentary characteristics. Ultra¬
violet radiation exposure is the predominant environmental risk factor for
melanoma. Recently, both rare high risk susceptibility genes and common
polymorphic genes contributing to melanoma risk have been identified.
Applications of Genomics in Melanoma Oncogene Discovery 397
Michael F. Berger and Levi A. Garraway
The identification of recurrent alterations in the melanoma genome has
provided key insights into the biology of melanoma genesis and progres¬
sion. These discoveries have come about as a result of the systematic de¬
ployment and integration of diverse genomic technologies, including DNA
sequencing, chromosomal copy number analysis, and gene expression
profiling. Here, the discoveries of several key melanoma oncogenes affect¬
ing critical cell pathways are described and the role played by evolving ge¬
nomics technologies in melanoma oncogene discovery is examined.
These advances are being exploited to improve prognosis and treatment
of melanoma patients through the development of genome-based diag¬
nostic and targeted therapeutic avenues.
Melanoma Genetics: An Update on Risk-Associated Genes 415
Durga Udayakumar and Hensin Tsao
The past 15 years have seen rapid advances in both our understanding of
hereditary melanoma genetics and the technologies that enable scientists
to make discoveries. Despite great efforts by many groups worldwide,
other high-risk melanoma loci besides CDKN2A still remain elusive. A
panel of polymorphisms that appears to confer low-to-moderate risk for
melanoma has been assembled through functional and genome-wide as¬
sociation studies. The goal of personalized melanoma risk prediction is
within our reach, although true clinical use has yet to be established.
Tumor Angiogenesis in Melanoma 431
Alexander G. Marneros
A large number of clinical studies are being conducted to assess the ef¬
fects of angiogenesis inhibitors in the treatment of patients who have
Contents
metastatic melanoma. It has become increasingly clear that a therapeutic
approach that combines angiogenesis inhibitors with cytotoxic agents or
other treatment modalities is more likely to result in a clinical benefit for pa¬
tients rather than antiangiogenesis treatments alone. However, a targeted
treatment approach with antiangiogenic agents needs to be based on an
in-depth understanding of the complex mechanisms involved in melanoma
tumor angiogenesis.
Transcriptional Regulation in Melanoma 447
Devarati Mitra and David E. Fisher
Transcriptional regulation in melanoma is a complex process that tends to
hijack the normal melanocyte signaling pathways involved in melanocyte
development, pigmentation, and survival. At the center of these often over¬
lapping networks of transcriptional activation and repression is micro-
phthalmia-associated transcription factor (MITF), a melanocyte lineage
marker that increases pigment production and exhibits diverse effects
on cell survival, proliferation, and cell cycle arrest. The particular condi¬
tions that allow MITF to produce these potentially contradictory roles
have not yet been fully elucidated, but analysis of the pathways involved
provides opportunities to learn about new therapeutic strategies.
Progress in Melanoma Histopathology and Diagnosis 467
Adriano Piris and Martin C. Mihm, Jr
This article reviews the main aspects of the histopathology of cutaneous
melanoma with emphasis on recent advances in the morphological evalu¬
ation of these lesions. The limitations of morphology for the so called
borderline lesions are briefly discussed, with a list of diagnostic criteria
to help predict behavior for these challenging lesions. The prognostic fac¬
tors are described with emphasis on the ones that are currently being used
by the American Joint Committee on Cancer staging system. Ancillary
tests, such as immunohistochemistry and molecular techniques, are also
briefly touched upon as complimentary tools to help understand the biol¬
ogy of malignant melanoma. The conclusion is that an accurate morpho¬
logical evaluation remains the most efficient approach to establish the
diagnosis and predict behavior of this challenging neoplasm.
Melanoma Early Detection 481
Vitaly Terushkin and Allan C. Halpern
Recognizing early forms of melanoma may have significant impact on de¬
creasing mortality from this malignancy. As a result, multiple efforts have
focused on developing new and improving current early detection strate¬
gies. These include educating patients about the importance of performing
skin self-examination, increasing rates of complete skin examinations by
physicians in the context of routine care, initiating mass screening cam¬
paigns, creating specialized skin cancer clinics, and developing better di¬
agnostic tools through advances in technology. In this article, the current
state of these efforts is reviewed.
Contents
The Classification of Cutaneous Melanoma 501
Lyn McDivitt Duncan
Forty years ago, a clinical and histological classification scheme and prog¬
nostic factors were described for cutaneous melanoma. This scheme in¬
cluded the subtypes superficial spreading, nodular and lentigo maligna,
and prognostic factors including tumor thickness, ulceration, and mitotic
activity. There have been some tweaks to the classification scheme, but
these basic findings form the foundation for melanoma diagnosis and
staging today. Currently, no molecular marker or target has proved reliably
useful in the staging or treatment of melanoma. Measurement with a simple
ruler serves as the basis for the staging of primary cutaneous melanoma,
while the recognition of primary tumor mitotic activity and ulceration also
remain significant factors. Recently, mutational analysis has revealed
a correlation of activating mutations with the morphological descriptors
from decades ago. Future classification schemes may have more power
in predicting response to therapy by integrating specific genomic and
intra-tumoral expression profiles with histologic findings.
Educational and Screening Campaigns to Reduce Deaths from Melanoma 515
Alan C. Geller
Many deaths of melanoma can be prevented through identification and
screening of persons at greatest risk of disease. Herein, we discuss vari¬
ous strategies to reduce avoidable mortality—including targeted screen¬
ing of persons with changing moles and middle-aged and older men of
lower socioeconomic status. We also propose the framework for a ran¬
domized screening trial for melanoma.
BRAF Signaling and Targeted Therapies in Melanoma 529
Nathalie Dhomen and Richard Marais
The RAS/RAF/MEK/ERK signaling pathway has emerged as a major player
in the induction and maintenance of melanoma, particularly the protein
kinase BRAF, mutated in approximately 44% of melanoma cases. The
availability of new drugs affecting the components of this pathway and
pathways that may cooperate with MAPK signaling, means that targeted
therapies are fast becoming a real option in the clinical management of
melanoma. The authors discuss what they learned from clinical trials using
first- and second-generation inhibitors to this pathway.
Melanoma and immunotherapy 547
Alexander M.M. Eggermont and Dirk Schadendorf
About 20% of all primary melanomas will spread. The likelihood of meta-
static behavior correlates with prognostic factors such as tumor thickness,
mitotic index, presence of ulceration, lymphocyte infiltration, age, gender,
and anatomic site. Immunotherapies are developed for melanoma patients
in stage IV who have distant metastases and in stage II to III patients in the
Contents
adjuvant micrometastatic setting, where only a fraction of patients have
widespread (microscopic) disease.
Surgical Management of Melanoma 565
Jennifer A. Wargo and Kenneth Tanabe
Melanoma is an increasing health care problem worldwide. Up to 80,000
cases of melanoma are diagnosed per year and it is the sixth leading cause
of cancer death in the United States. The lifetime risk is estimated to be 1 in
75 individuals for the development of melanoma. Surgery remains the
mainstay of treatment of melanoma, and in most cases it is curative. Sev¬
eral important surgical issues are discussed in this review, including the
extent of surgical margins, Mohs micrographic surgery for melanoma in
situ, the use of sentinel lymph node biopsy, the usefulness of lymphade-
nectomy, isolated limb perfusion, and the role of metastasectomy.
The History and Future of Chemotherapy for Melanoma 583
Arvin S. Yang and Paul B. Chapman
Melanoma is considered a chemotherapy-resistant cancer, but in reality
there are several chemotherapy drugs with significant single-agent activ¬
ity. Response rates to combination regimens are reproducibly higher
than with standard dacarbazine, but of the randomized trials comparing
combination regimens with dacarbazine, none were of sufficient size to de¬
tect a realistic effect on survival. Similarly, adjuvant chemotherapy has not
had a realistic test in melanoma. Response to chemotherapy is associated
reproducibly with better survival rates suggesting that regimens with higher
response rates are needed. Recent observations suggest that combining
antiangiogenic agents with either dacarbazine or temozolomide can dou¬
ble response rates. These combinations are worthy of further investiga¬
tion and might serve as a foundation on which to build a combination
regimen that improves overall survival in metastatic melanoma patients.
Drug Targeting of Oncogenic Pathways in Melanoma 599
Leslie A. Fecher, Ravi K. Amaravadi, Lynn M. Schuchter, and Keith T. Flaherty
Melanoma continues to be one of the most aggressive and morbid malig¬
nancies once metastatic. Overall survival for advanced unresectable mel¬
anoma has not changed over the past several decades. However, the
presence of some long-term survivors of metastatic melanoma highlights
the heterogeneity of this disease and the potential for improved outcomes.
Current research is uncovering the molecular and genetic scaffolding of
normal and aberrant cell function. The known oncogenic pathways in mel¬
anoma and the attempts to develop therapy for them are discussed. The
targeting of certain cellular processes, downstream of the common ge¬
netic alterations, for which the issues of target and drug validation are
somewhat distinct, are also highlighted.
Index 619
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| title | Advances in melanoma |
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| title_full | Advances in melanoma guest ed. David E. Fisher |
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| title_short | Advances in melanoma |
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