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Melanoma: HELP
Articles by Hensin Tsao
Based on 83 articles published since 2008
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Between 2008 and 2019, H. Tsao wrote the following 83 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Guideline Guidelines of care for the management of primary cutaneous melanoma. 2019

Swetter, Susan M / Tsao, Hensin / Bichakjian, Christopher K / Curiel-Lewandrowski, Clara / Elder, David E / Gershenwald, Jeffrey E / Guild, Valerie / Grant-Kels, Jane M / Halpern, Allan C / Johnson, Timothy M / Sober, Arthur J / Thompson, John A / Wisco, Oliver J / Wyatt, Samantha / Hu, Shasa / Lamina, Toyin. ·Department of Dermatology, Stanford University Medical Center and Cancer Institute, Stanford, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California. Electronic address: sswetter@stanford.edu. · Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Wellman Center for Photomedicine, Boston, Massachusetts. · Department of Dermatology, University of Michigan Health System, Ann Arbor, Michigan; Comprehensive Cancer Center, Ann Arbor, Michigan. · Division of Dermatology, University of Arizona, Tucson, Arizona; University of Arizona Cancer Center, Tucson, Arizona. · Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. · AIM at Melanoma Foundation, Plano, Texas. · Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut; Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut; Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut. · Department of Dermatology, Memorial Sloan-Kettering Cancer Center, New York, New York. · Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Division of Oncology, University of Washington, Seattle, Washington; Seattle Cancer Care Alliance, Seattle, Washington. · Department of Dermatology, Oregon Health and Science University, Portland, Oregon. · Decatur Dermatology, Decatur, Alabama. · Department of Dermatology, University of Miami Health System, Miami, Florida. · American Academy of Dermatology, Rosemont, Illinois. ·J Am Acad Dermatol · Pubmed #30392755.

ABSTRACT: The incidence of primary cutaneous melanoma continues to increase each year. Melanoma accounts for the majority of skin cancer-related deaths, but treatment is usually curative following early detection of disease. In this American Academy of Dermatology clinical practice guideline, updated treatment recommendations are provided for patients with primary cutaneous melanoma (American Joint Committee on Cancer stages 0-IIC and pathologic stage III by virtue of a positive sentinel lymph node biopsy). Biopsy techniques for a lesion that is clinically suggestive of melanoma are reviewed, as are recommendations for the histopathologic interpretation of cutaneous melanoma. The use of laboratory, molecular, and imaging tests is examined in the initial work-up of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, recommendations for surgical margins and the concepts of staged excision (including Mohs micrographic surgery) and nonsurgical treatments for melanoma in situ, lentigo maligna type (including topical imiquimod and radiation therapy), are updated. The role of sentinel lymph node biopsy as a staging technique for cutaneous melanoma is described, with recommendations for its use in clinical practice. Finally, current data regarding pregnancy and melanoma, genetic testing for familial melanoma, and management of dermatologic toxicities related to novel targeted agents and immunotherapies for patients with advanced disease are summarized.

2 Guideline Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology. 2011

Bichakjian, Christopher K / Halpern, Allan C / Johnson, Timothy M / Foote Hood, Antoinette / Grichnik, James M / Swetter, Susan M / Tsao, Hensin / Barbosa, Victoria Holloway / Chuang, Tsu-Yi / Duvic, Madeleine / Ho, Vincent C / Sober, Arthur J / Beutner, Karl R / Bhushan, Reva / Smith Begolka, Wendy / Anonymous6410703. ·Department of Dermatology, University of Michigan Health System and Comprehensive Cancer Center, Ann Arbor, Michigan, USA. ·J Am Acad Dermatol · Pubmed #21868127.

ABSTRACT: The incidence of primary cutaneous melanoma has been increasing dramatically for several decades. Melanoma accounts for the majority of skin cancer-related deaths, but treatment is nearly always curative with early detection of disease. In this update of the guidelines of care, we will discuss the treatment of patients with primary cutaneous melanoma. We will discuss biopsy techniques of a lesion clinically suspicious for melanoma and offer recommendations for the histopathologic interpretation of cutaneous melanoma. We will offer recommendations for the use of laboratory and imaging tests in the initial workup of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, we will provide recommendations for surgical margins and briefly discuss nonsurgical treatments. Finally, we will discuss the value and limitations of sentinel lymph node biopsy and offer recommendations for its use in patients with primary cutaneous melanoma.

3 Editorial Visual Inspection and the US Preventive Services Task Force Recommendation on Skin Cancer Screening. 2016

Tsao, Hensin / Weinstock, Martin A. ·Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Boston. · Department of Dermatology, Warren Alpert Medical School of Brown University, Providence, Rhode Island3Division of Dermatology, Veterans Affairs Medical Center, Providence, Rhode Island. ·JAMA · Pubmed #27458944.

ABSTRACT: -- No abstract --

4 Editorial Melanoma-associated naevi: precursors or coincidence? 2015

Kraft, S / Tsao, H. ·Dermatopathology Service, Massachusetts General Hospital, Harvard Medical School, Boston, MA, U.S.A. skraft@mgh.harvard.edu. · Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, U.S.A. htsao@mgh.harvard.edu. ·Br J Dermatol · Pubmed #26404570.

ABSTRACT: -- No abstract --

5 Editorial Targeted Therapies in Melanoma: Translational Research at Its Finest. 2015

Ho, Allen W / Tsao, Hensin. ·Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA. · Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA. Electronic address: htsao@partners.org. ·J Invest Dermatol · Pubmed #26174532.

ABSTRACT: -- No abstract --

6 Editorial Opening the melanoma black box. 2014

Tsao, H. ·Department of Dermatology, Massachusetts General Hospital, Boston, MA, U.S.A. htsao@partners.org. ·Br J Dermatol · Pubmed #24443911.

ABSTRACT: -- No abstract --

7 Review Genotypic and Phenotypic Features of BAP1 Cancer Syndrome: A Report of 8 New Families and Review of Cases in the Literature. 2017

Haugh, Alexandra M / Njauw, Ching-Ni / Bubley, Jeffrey A / Verzì, Anna Elisa / Zhang, Bin / Kudalkar, Emily / VandenBoom, Timothy / Walton, Kara / Swick, Brian L / Kumar, Raj / Rana, Huma Q / Cochrane, Sarah / McCormick, Shelley R / Shea, Christopher R / Tsao, Hensin / Gerami, Pedram. ·Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Massachusetts General Hospital Cancer Center, Boston. · Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Boston. · Department of Dermatology, University of Iowa Hospitals and Clinics, and Iowa City VAMC, Iowa City. · Dana Farber Cancer Institute, Boston, Massachusettss. · Section of Dermatology, University of Chicago Medicine, Chicago, Illinois. · The Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois. ·JAMA Dermatol · Pubmed #28793149.

ABSTRACT: Importance: Patients with germline mutations in BAP1 may develop several flesh-colored melanocytic BAP1-mutated atypical intradermal tumors (MBAITs). These tumors generally develop earlier than other BAP1-associated tumors, highlighting an important role for dermatologists in identifying and screening patients with a history suggestive of a germline mutation. Objective: To describe 8 new families with germline mutations in BAP1 and provide a comprehensive review of reported cases. Design, Settings and Participants: Patients were identified in an outpatient dermatology clinical setting over a 6-month period (10 mutation carriers from 8 families) and through a literature review using PubMed (205 patients). Exposures: Mutations were identified through next-generation sequencing of saliva or blood samples, and RNA was extracted from fibroblasts cultured from a patient with an intronic variant to determine the impact of the mutation on the coding sequence. Main Outcomes and Measures: All 215 patients were assessed for personal and/or family history and genotype. These findings were compiled and assessed for any association between genotype and phenotype. Results: Overall, this study included 215 patients (108 women, 91 men, and 16 gender unspecified; median [range] age, 46.5 [10.0-79.0] years). Nine of the 10 patients who were identified in the outpatient dermatology setting were found to have MBAITs on clinical examination. Forty of 53 patients (75%) identified in the literature review who underwent total-body skin examinations (TBSE) were found to have MBAITs, suggesting a high penetrance in patients who have undergone TBSE. The most prevalent malignancies among BAP1 mutation carriers were uveal melanoma (n =  60 [28%]), mesothelioma (n = 48 [22%]), cutaneous melanoma (n = 38 [18%]), and renal cell carcinoma (n = 20 [9%]). A total of 71 unique mutations in BAP1 have been reported. Conclusions and Relevance: Our results indicate that germline mutations in both coding and noncoding regions throughout the BAP1 gene can impair protein function, leading to an increased risk for several associated malignancies. Four of the 8 probands we present had no history of BAP1-associated malignancies and were assessed for germline mutations when found to have MBAITs on dermatologic examination. Dermatologists can identify patients with a high likelihood of the BAP1 cancer syndrome through personal and family history and TBSE for the presence of possible MBAITs.

8 Review Somatic driver mutations in melanoma. 2017

Reddy, Bobby Y / Miller, David M / Tsao, Hensin. ·Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. ·Cancer · Pubmed #28543693.

ABSTRACT: Melanoma has one of the highest somatic mutational burdens among solid malignancies. Although the rapid progress in genomic research has contributed immensely to our understanding of the pathogenesis of melanoma, the clinical significance of the vast array of genomic alterations discovered by next-generation sequencing is far from being fully characterized. Most mutations prevalent in melanoma are simply neutral "passengers," which accompany functionally significant "drivers" under transforming conditions. The delineation of driver mutations from passenger mutations is critical to the development of targeted therapies. Novel advances in genomic data analysis have aided in distinguishing true driver mutations involved in tumor progression. Here, the authors review the current literature on important somatic driver mutations in melanoma, along with the implications for treatment. Cancer 2017;123:2104-17. © 2017 American Cancer Society.

9 Review Recent Advances in Melanoma and Melanocyte Biology. 2017

Tsao, Hensin / Fukunaga-Kalabis, Mizuho / Herlyn, Meenhard. ·Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA. Electronic address: htsao@partners.org. · Molecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania, USA. · Molecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania, USA. Electronic address: herlynm@wistar.org. ·J Invest Dermatol · Pubmed #28089201.

ABSTRACT: -- No abstract --

10 Review Hereditary melanoma: Update on syndromes and management: Emerging melanoma cancer complexes and genetic counseling. 2016

Soura, Efthymia / Eliades, Philip J / Shannon, Kristen / Stratigos, Alexander J / Tsao, Hensin. ·1st Department of Dermatology, University Clinic, "Andreas Sygros" Hospital, Athens, Greece. · Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts; Tufts University School of Medicine, Boston, Massachusetts. · Melanoma Genetics Program/MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts. · Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts; Melanoma Genetics Program/MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: htsao@partners.org. ·J Am Acad Dermatol · Pubmed #26892651.

ABSTRACT: Recent advances in cancer genomics have enabled the discovery of many cancer-predisposing genes that are being used to classify new familial melanoma/cancer syndromes. In addition to CDKN2A and CDK4, germline variants in TERT, MITF, and BAP1 have been added to the list of genes harboring melanoma-predisposing mutations. These newer entities may have escaped earlier description in part because of more advanced technologies now being used and in part because of their mixed cancer phenotype as opposed to a melanoma-focused syndrome. Dermatologists should be aware of (and be able to recognize) the clinical signs in high-risk patients in different contexts. Personal and family histories of cancer should always be sought in patients with multiple nevi or a positive history for melanoma, and should be updated annually. Various features that are unique to specific disorders, such as the appearance of melanocytic BAP1-mutated atypical intradermal tumors in cases of BAP1 melanoma syndrome, should also be recognized early. These patients should be offered regular screenings with the use of dermoscopy and total body photography, as needed. More importantly, referral to other specialists may be needed if a risk for internal malignancy is suspected. It is important to have in mind that these patients tend to develop multiple melanomas, along with various internal organ malignancies, often at younger ages; a multidisciplinary approach to their cancer screening and treatment is ideal.

11 Review Hereditary melanoma: Update on syndromes and management: Genetics of familial atypical multiple mole melanoma syndrome. 2016

Soura, Efthymia / Eliades, Philip J / Shannon, Kristen / Stratigos, Alexander J / Tsao, Hensin. ·1st Department of Dermatology, University Clinic, "Andreas Sygros" Hospital, Athens, Greece. · Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts; Tufts University School of Medicine, Boston, Massachusetts. · Melanoma Genetics Program/MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts. · Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts; Melanoma Genetics Program/MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: htsao@partners.org. ·J Am Acad Dermatol · Pubmed #26892650.

ABSTRACT: Malignant melanoma is considered the most lethal skin cancer if it is not detected and treated during its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (ie, unilateral lineage, multigenerational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. These patients have a high risk of developing multiple primary melanomas and internal organ malignancies, especially pancreatic cancer; therefore, a multidisciplinary approach is necessary in many cases. The value of dermoscopic examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first-degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. This must be performed with care, however, and only by qualified individuals trained in cancer risk analysis.

12 Review Early detection of melanoma: reviewing the ABCDEs. 2015

Anonymous4130821 / Tsao, Hensin / Olazagasti, Jeannette M / Cordoro, Kelly M / Brewer, Jerry D / Taylor, Susan C / Bordeaux, Jeremy S / Chren, Mary-Margaret / Sober, Arthur J / Tegeler, Connie / Bhushan, Reva / Begolka, Wendy Smith. ·Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Dermatology, Mayo Clinic, Rochester, Minnesota; School of Medicine, University of Puerto Rico, San Juan, Puerto Rico. · Department of Dermatology, University of California, San Francisco, California. · Society Hill Dermatology and Cosmetic Center, Philadelphia, Pennsylvania. · Department of Dermatology, University Hospitals Case Medical Center, and Case Western Reserve University School of Medicine, Cleveland, Ohio. · Department of Dermatology, University of California, San Francisco, California; Dermatology Service, San Francisco Veterans Affairs Medical Center, San Francisco, California. · American Academy of Dermatology, Schaumburg, Illinois. · American Academy of Dermatology, Schaumburg, Illinois. Electronic address: wsmithbegolka@aad.org. ·J Am Acad Dermatol · Pubmed #25698455.

ABSTRACT: Over the course of their nearly 30-year history, the ABCD(E) criteria have been used globally in medical education and in the lay press to provide simple parameters for assessment of pigmented lesions that need to be further evaluated by a dermatologist. In this article, the efficacy and limitations of the ABCDE criteria as both a clinical tool and a public message will be reviewed.

13 Review Melanoma: clinical features and genomic insights. 2014

Hawryluk, Elena B / Tsao, Hensin. ·Dermatology Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115 Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114. · Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114. ·Cold Spring Harb Perspect Med · Pubmed #25183853.

ABSTRACT: Recent efforts in genomic research have enabled the characterization of molecular mechanisms underlying many types of cancers, ushering novel approaches for diagnosis and therapeutics. Melanoma is a molecularly heterogeneous disease, as many genetic alterations have been identified and the clinical features can vary. Although discoveries of frequent mutations including BRAF have already made clinically significant impact on patient care, there is a growing body of literature suggesting a role for additional mutations, driver and passenger types, in disease pathophysiology. Although some mutations have been strongly associated with clinical phenotypes of melanomas (such as physical distribution or morphologic subtype), the function or implications of many of the recently identified mutations remains less clear. The phenotypic and clinical impact of genomic mutations in melanoma remains a promising opportunity for progress in the care of melanoma patients.

14 Review Current status and future directions of molecularly targeted therapies and immunotherapies for melanoma. 2014

Miller, David M / Flaherty, Keith T / Tsao, Hensin. ·Wellman Center for Photomedicine and Department of Dermatology, MGH Cancer Center, Massachusetts General Hospital, MA USA. E-mail: htsao@partners.org. ·Semin Cutan Med Surg · Pubmed #25085663.

ABSTRACT: Key molecular and immunological insights over the past decade have radically changed the face of therapy in melanoma. Whereas 5 years ago, treatment for advanced melanoma was restricted to the alkylating agent dacarbazine and the immunostimulants interleukin-2 and interferon-α-2b, today the therapeutic menu includes precise therapies that target key determinants in oncogenic pathways and immune checkpoints. In this chapter, we will review the current status and future directions of targeted therapies for melanoma directed at mitogen-activated pathways and immune checkpoints.

15 Review Melanoma susceptibility genes and risk assessment. 2014

Marzuka-Alcalá, Alexander / Gabree, Michele Jacobs / Tsao, Hensin. ·Yale School of Medicine, New Haven, CT, USA. ·Methods Mol Biol · Pubmed #24258989.

ABSTRACT: Familial melanoma accounts for approximately a tenth of all melanoma cases. The most commonly known melanoma susceptibility gene is the highly penetrant CDKN2A (p16INK4a) locus, which is transmitted in an autosomal dominant fashion and accounts for approximately 20-50 % of familial melanoma cases. Mutated p16INK4a shows impaired capacity to inhibit the cyclin D1-CDK4 complex, allowing for unchecked cell cycle progression. Mutations in the second protein coded by CDKN2A, p14ARF, are much less common and result in proteasomal degradation of p53 with subsequent accumulation of DNA damage as the cell progresses through the cell cycle without a functional p53-mediated DNA damage response. Mutations in CDK4 that impair the inhibitory interaction with p16INK4a also increase melanoma risk but these mutations are extremely rare. Genes of the melanin biosynthetic pathway, including MC1R and MITF, have also been implicated in melanomagenesis. MC1R variants were traditionally thought to increase risk for melanoma secondary to intensified UV-mediated DNA damage in the setting of absent photoprotective eumelanin. Accumulation of pheomelanin, which appears to have a carcinogenic effect regardless of UV exposure, may be a more likely mechanism. Impaired SUMOylation of the E318K variant of MITF results in increased transcription of genes that confer melanocytes with a pro-malignant phenotype. Mutations in the tumor suppressor BAP1 enhance the metastatic potential of uveal melanoma and predispose to cutaneous/ocular melanoma, atypical melanocytic tumors, and other internal malignancies (COMMON syndrome). Genome-wide association studies have identified numerous low-risk alleles. Although several melanoma susceptibility genes have been identified, risk assessment tools have been developed only for the most common gene implicated with hereditary melanoma, CDKN2A. MelaPRO, a validated model that relies on Mendelian inheritance and Bayesian probability theories, estimates carrier probability for CDKN2A and future risk of melanoma taking into account a patient's family and past medical history of melanoma. Genetic testing for CDKN2A mutations is currently available but the Melanoma Genetics Consortium recommends offering such testing to patients only in the context of research protocols because clinical utility is uncertain.

16 Review Melanoma genetics: the other side. 2013

Bis, Sabina / Tsao, Hensin. ·Department of Dermatology, Harvard Medical School, Boston, MA 02114, USA. ·Clin Dermatol · Pubmed #23438378.

ABSTRACT: Although melanoma has traditionally been regarded as a uniformly fatal malignancy, personalized treatment of this cancer relies on the recognition of its genetic heterogeneity and our ability to pharmacologically target these specific and recurrent changes. Recent advances in the treatment of melanoma have come from the understanding that melanoma is a large family of molecularly distinct diseases. Advances in melanoma genetics and new molecular technology, such as whole-exome and whole-genome sequencing, have lead to unprecedented progress in understanding the key oncogenes and signaling pathways involved in the pathogenesis and progression of melanoma. In addition, we have gained an appreciation for the complexity of such a system with numerous points of cross talk, which has partially impeded our current therapeutic strategies in patients with advanced melanoma. In this review, we focus on the novel discoveries in melanoma genetics and the potential for therapeutic options.

17 Review Melanoma: from mutations to medicine. 2012

Tsao, Hensin / Chin, Lynda / Garraway, Levi A / Fisher, David E. ·Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ·Genes Dev · Pubmed #22661227.

ABSTRACT: Melanoma is often considered one of the most aggressive and treatment-resistant human cancers. It is a disease that, due to the presence of melanin pigment, was accurately diagnosed earlier than most other malignancies and that has been subjected to countless therapeutic strategies. Aside from early surgical resection, no therapeutic modality has been found to afford a high likelihood of curative outcome. However, discoveries reported in recent years have revealed a near avalanche of breakthroughs in the melanoma field-breakthroughs that span fundamental understanding of the molecular basis of the disease all the way to new therapeutic strategies that produce unquestionable clinical benefit. These discoveries have been born from the successful fruits of numerous researchers working in many-sometimes-related, although also distinct-biomedical disciplines. Discoveries of frequent mutations involving BRAF(V600E), developmental and oncogenic roles for the microphthalmia-associated transcription factor (MITF) pathway, clinical efficacy of BRAF-targeted small molecules, and emerging mechanisms underlying resistance to targeted therapeutics represent just a sample of the findings that have created a striking inflection in the quest for clinically meaningful progress in the melanoma field.

18 Review Melanoma: new insights and new therapies. 2012

Nikolaou, Vasiliki A / Stratigos, Alexander J / Flaherty, Keith T / Tsao, Hensin. ·Dermato-Oncology Unit, Department of Dermatology, University of Athens Medical School, Andreas Sygros Hospital, Athens, Greece. ·J Invest Dermatol · Pubmed #22217739.

ABSTRACT: Metastatic melanoma has historically been considered as one of the most therapeutically challenging malignancies. However, for the first time after decades of basic research and clinical investigation, new drugs have produced major clinical responses. The discovery of BRAF mutations in melanoma created the first opportunity to develop oncogene-directed therapy in this disease and led to the development of compounds that inhibit aberrant BRAF activity. A decade later, vemurafenib, an orally available and well-tolerated selective BRAF inhibitor, ushered in a new era of molecular treatments for advanced disease. Additional targets have been identified, and novel agents that impact on various signaling pathways or modulate the immune system hold the promise of a whole new therapeutic landscape for patients with metastatic melanoma. One of the major thrusts in melanoma therapy is now focused on understanding and targeting the network of signal transduction pathways and on attacking elements that underlie the tumor's propensity for growth and chemoresistance. In this article, we review the novel targeted anticancer approaches that are under consideration in melanoma treatment.

19 Review Targeting the RAS pathway in melanoma. 2012

Ji, Zhenyu / Flaherty, Keith T / Tsao, Hensin. ·Wellman Center for Photomedicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. ·Trends Mol Med · Pubmed #21962474.

ABSTRACT: Metastatic melanoma is a highly lethal type of skin cancer and is often refractory to all traditional chemotherapeutic agents. Key insights into the genetic makeup of melanoma tumors have led to the development of promising targeted agents. An activated RAS pathway, anchored by oncogenic BRAF, appears to be the central motor driving melanoma proliferation. Although recent clinical trials have brought enormous hope to patients with melanoma, adverse effects and novel escape mechanisms of these inhibitors have already emerged. Definition of the limits of the first successful targeted therapies will provide the basis for further advances in management of disseminated melanoma. In this review, the current state of targeted therapy for melanoma is discussed, including the potent BRAF(V600E) inhibitor vemurafenib.

20 Review Comprehensive field synopsis and systematic meta-analyses of genetic association studies in cutaneous melanoma. 2011

Chatzinasiou, Foteini / Lill, Christina M / Kypreou, Katerina / Stefanaki, Irene / Nicolaou, Vasiliki / Spyrou, George / Evangelou, Evangelos / Roehr, Johannes T / Kodela, Elizabeth / Katsambas, Andreas / Tsao, Hensin / Ioannidis, John P A / Bertram, Lars / Stratigos, Alexander J. ·Department of Dermatology, University of Athens Medical School, Andreas Sygros Hospital, Dragoumi 5, Athens 161 21, Greece. ·J Natl Cancer Inst · Pubmed #21693730.

ABSTRACT: BACKGROUND: Although genetic studies have reported a number of loci associated with cutaneous melanoma (CM) risk, a comprehensive synopsis of genetic association studies published in the field and systematic meta-analysis for all eligible polymorphisms have not been reported. METHODS: We systematically annotated data from all genetic association studies published in the CM field (n = 145), including data from genome-wide association studies (GWAS), and performed random-effects meta-analyses across all eligible polymorphisms on the basis of four or more independent case-control datasets in the main analyses. Supplementary analyses of three available datasets derived from GWAS and GWAS-replication studies were also done. Nominally statistically significant associations between polymorphisms and CM were graded for the strength of epidemiological evidence on the basis of the Human Genome Epidemiology Network Venice criteria. All statistical tests were two-sided. RESULTS: Forty-two polymorphisms across 18 independent loci evaluated in four or more datasets including candidate gene studies and available GWAS data were subjected to meta-analysis. Eight loci were identified in the main meta-analyses as being associated with a risk of CM (P < .05) of which four loci showed a genome-wide statistically significant association (P < 1 × 10(-7)), including 16q24.3 (MC1R), 20q11.22 (MYH7B/PIGU/ASIP), 11q14.3 (TYR), and 5p13.2 (SLC45A2). Grading of the cumulative evidence by the Venice criteria suggested strong epidemiological credibility for all four loci with genome-wide statistical significance and one additional gene at 9p23 (TYRP1). In the supplementary meta-analyses, a locus at 9p21.3 (CDKN2A/MTAP) reached genome-wide statistical significance with CM and had strong epidemiological credibility. CONCLUSIONS: To the best of our knowledge, this is the first comprehensive field synopsis and systematic meta-analysis to identify genes associated with an increased susceptibility to CM.

21 Review Pathways to melanoma. 2010

Ko, Justin M / Velez, Nicole F / Tsao, Hensin. ·Department of Dermatology, Harvard Medical School, Boston, MA, USA. ·Semin Cutan Med Surg · Pubmed #21277534.

ABSTRACT: Melanoma is one of the most aggressive and yet poorly understood of human malignancies. Advances in genomics has allowed a more nuanced understanding of the disease, moving beyond the traditional dysplastic nevus-to-melanoma model and identifying multiple divergent oncogenic pathways leading to melanoma. An understanding of the molecular mechanisms driving melanoma has opened the doors for the development of targeted therapeutic approaches. As we enter the era of personalized medicine, it will be critical for clinicians to both appreciate and be able to determine the molecular profile of their patients' melanoma because this profile will guide risk stratification, genetic counseling, and treatment customization. A review of the divergent pathways of melanoma development is presented here, with a particular emphasis on recently identified mutations, and their implications for patient care.

22 Review Genetic determinants of cutaneous melanoma predisposition. 2010

Udayakumar, Durga / Mahato, Bisundev / Gabree, Michele / Tsao, Hensin. ·Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA. ·Semin Cutan Med Surg · Pubmed #21051013.

ABSTRACT: In the last 2 decades, advances in genomic technologies and molecular biology have accelerated the identification of multiple genetic loci that confer risk for cutaneous melanoma. The risk alleles range from rarely occurring, high-risk variants with a strong familial predisposition to low-risk to moderate-risk variants with modest melanoma association. Although the high-risk alleles are limited to the CDKN2A and CDK4 loci, the authors of recent genome-wide association studies have uncovered a set of variants in pigmentation loci that contribute to low risk. A biological validation of these new findings would provide greater understanding of the disease. In this review we describe some of the important risk loci and their association to risk of developing cutaneous melanoma and also address the current clinical challenges in CDKN2A genetic testing.

23 Review Molecular therapeutic approaches to melanoma. 2010

Ji, Zhenyu / Flaherty, Keith T / Tsao, Hensin. ·Wellman Center for Photomedicine/Dept of Dermatology, 55 Fruit Street, Boston, MA 02114, USA. ·Mol Aspects Med · Pubmed #20176049.

ABSTRACT: Metastatic melanoma is a highly lethal cancer that has historically been refractory to all tested pharmacological agents. An understanding of the mechanisms responsible for its oncogenesis is critical for developing successful therapies. An enormous amount of data generated over the last few decades have revealed important biological insights into melanoma initiation, progression and maintenance, which bring new directions and approaches to treatment of this devastating skin cancer.

24 Review Selection criteria for genetic assessment of patients with familial melanoma. 2009

Leachman, Sancy A / Carucci, John / Kohlmann, Wendy / Banks, Kimberly C / Asgari, Maryam M / Bergman, Wilma / Bianchi-Scarrà, Giovanna / Brentnall, Teresa / Bressac-de Paillerets, Brigitte / Bruno, William / Curiel-Lewandrowski, Clara / de Snoo, Femke A / Debniak, Tadeusz / Demierre, Marie-France / Elder, David / Goldstein, Alisa M / Grant-Kels, Jane / Halpern, Allan C / Ingvar, Christian / Kefford, Richard F / Lang, Julie / MacKie, Rona M / Mann, Graham J / Mueller, Kurt / Newton-Bishop, Julia / Olsson, Håkan / Petersen, Gloria M / Puig, Susana / Rigel, Darrell / Swetter, Susan M / Tucker, Margaret A / Yakobson, Emanuel / Zitelli, John A / Tsao, Hensin. ·Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112-5550, USA. sancy.leachman@hci.utah.edu ·J Am Acad Dermatol · Pubmed #19751883.

ABSTRACT: Approximately 5% to 10% of melanoma may be hereditary in nature, and about 2% of melanoma can be specifically attributed to pathogenic germline mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A). To appropriately identify the small proportion of patients who benefit most from referral to a genetics specialist for consideration of genetic testing for CDKN2A, we have reviewed available published studies of CDKN2A mutation analysis in cohorts with invasive, cutaneous melanoma and found variability in the rate of CDKN2A mutations based on geography, ethnicity, and the type of study and eligibility criteria used. Except in regions of high melanoma incidence, such as Australia, we found higher rates of CDKN2A positivity in individuals with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family. The work summarized in this review should help identify individuals who are appropriate candidates for referral for genetic consultation and possible testing.

25 Review Melanoma genetics: an update on risk-associated genes. 2009

Udayakumar, Durga / Tsao, Hensin. ·Department of Dermatology, Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, Edwards 211, 50 Blossom Street, Boston, MA 02114, USA. ·Hematol Oncol Clin North Am · Pubmed #19464594.

ABSTRACT: 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 association studies. The goal of personalized melanoma risk prediction is within our reach, although true clinical use has yet to be established.

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