AACR, Author Interviews, Melanoma, Wistar / 20.04.2015

Adina Vultur, Ph.D. Staff Scientist Meenhard Herlyn Laboratory Melanoma Research Center The Wistar Institute, PhiladelphiaMedicalResearch.com Interview with: Adina Vultur, Ph.D. Staff Scientist Meenhard Herlyn Laboratory Melanoma Research Center The Wistar Institute, Philadelphia Medical Research: What is the background for this study? What are the main findings? Dr. Vulture: Our goal was to identify new drugs with anti-melanoma activity but with minor effects on normal cells. We screened structurally distinct kinase inhibitors first, against multiple cell lines and normal cells, and identified the organometallic compound SM200 as being the most effective and selective molecule, capable of halting melanoma cell growth and invasion. Further characterization of SM200 indicated that PIM kinases are highly inhibited by this compound compared to other targets. We then confirmed the contribution of PIM kinases to melanoma pathobiology by knockdown studies and by using a clinically available PIM-inhibitor. Encouraging results with PIM kinase inhibition in multiple melanoma models including xenografts suggests that this could be a useful strategy against melanoma. (more…)
Author Interviews, Genetic Research, JAMA, Melanoma / 10.04.2015

Nancy E. Thomas, MD, PhD Department of Dermatology University of North CarolinaMedicalResearch.com Interview with: Nancy E. Thomas, MD, PhD Department of Dermatology University of North Carolina MedicalResearch: What is the background for this study? Dr. Thomas: BRAF and NRAS mutations found in melanomas are important for tumor initiation and maintenance. There are drugs that target BRAF mutations or the pathway that are approved for BRAF-mutant metastatic melanoma and help improve survival. However, it remains unknown whether these mutations in primary melanoma are markers for melanomas with a worse prognosis. MedicalResearch: What are the main findings? Dr. Thomas:
  • In a large international population-based study, we found that of primary melanomas, 30% harbor BRAF mutations, 13% have NRAS mutations and the other 57% do not have these mutations (wildtype).
  • In higher primary tumor stage melanomas, BRAF or NRAS mutations were associated with an approximately 3-fold increased rate of death from melanoma compared to wildtype melanoma adjusted for other prognostic factors.
  • Primary melanomas with NRAS mutations were less likely to have tumor infiltrating lymphocytes (TILs) in the tumor microenvironment. (more…)
Author Interviews, Brigham & Women's - Harvard, Melanoma, Surgical Research / 02.04.2015

MedicalResearch.com Interview with: Lyn McDivitt Duncan, MD Professor of Pathology, Harvard Medical School Chief, Dermatopathology Unit and Su Luo, MD Dermatology Resident Massachusetts General Hospital Boston, MA 02114 Medical Research: What is the background for this study? What are the main findings? Response: We studied 475 patients with cutaneous melanoma diagnosed at the Massachusetts General Hospital (MGH) who also had a sentinel lymph node biopsy procedure performed.  There is a practice gap in the sentinel lymph node biopsy procedure ranging from removal of one “sentinel” lymph node to removing the hottest lymph node and any lymph nodes with radioactive tracer of 10% or more of the hottest lymph node’s counts (with an average of three lymph nodes removed).  At the MGH we use this latter method.  We examined the sentinel lymph nodes in each case to determine whether the positive cases with microscopic melanoma metastases had metastases only in the most radioactive, or "hottest", node or whether tumor was also present in the less hot nodes. We found that in 19% of positive cases there were metastases present only in the less hot nodes. We also performed survival analysis and showed that the less hot nodal positive cases are of equivalent prognostic significance.  We found that removal of only the hottest lymph node would have led to under-staging of 19% of patients with melanoma. (more…)
Author Interviews, Dermatology, Melanoma, Stanford / 26.03.2015

Susan Swetter, MD Professor of Dermatology and Director, Pigmented Lesion and Melanoma Program Stanford University Medical Center and Cancer Institute.MedicalResearch.com Interview with: Susan Swetter, MD Professor of Dermatology and Director, Pigmented Lesion and Melanoma Program Stanford University Medical Center and Cancer Institute.   Medical Research: What is the background for this study? Dr. Swetter: This retrospective cohort study sought to explore the role of the topical immunomodular - imiquimod 5% cream - as both primary and adjuvant therapy (following optimal surgery) for patients with the lentigo maligna subtype of melanoma in situ. Assessment of alternative treatments to surgery for this melanoma in situ subtype are warranted given the increasing incidence of lentigo maligna in older, fair-complexioned individuals in the United States. Surgical management of lentigo maligna is complicated by its location on cosmetically sensitive areas such as the face, histologic differentiation between lentigo maligna and actinic melanocytic hyperplasia in chronically sun-damaged skin, and potential surgical complications in the elderly who may have medical co-morbid conditions. Medical Research: What are the main findings? Dr. Swetter: We conducted a retrospective review of 63 cases of lentigo maligna in 61 patients (mean age 71.1 years) who used topical 5% imiquimod cream instead of surgery (22 of 63 cases, 34.9%) or as an adjuvant therapy following attempted complete excision (63 cases, 65.1%), in which no clinical residual tumor was present but the histologic margins were transected or deemed narrowly excised. Our study showed overall clinical clearance of 86.2% in the 58 patients analyzed for local recurrence at a mean of 42.1 months of follow-up (standard deviation 27.4 months), with primarily treated cases demonstrating 72.7% clearance at a mean of 39.7 months (standard deviation 23.9 months), and adjuvant cases showing 94.4% clearance at a mean of 39.7 months (standard deviation 23.9 months).  We found a statistically significant association between imiquimod-induced inflammation and clinical or histologic clearance in primary but not adjuvant cases, although this latter finding may be explained by a lack of residual atypical melanocytes or true LM in the adjuvant setting, in which wide local excision had already been performed. (more…)
Author Interviews, Melanoma, Wistar / 19.03.2015

Russel E. Kaufman, MD President Emeritus Professor, Molecular and Cellular Oncogenesis Program Molecular and Cellular Oncogenesis Program The Wistar InstituteMedicalResearch.com Interview with: Russel E. Kaufman, MD President Emeritus Professor, Molecular and Cellular Oncogenesis Program Molecular and Cellular Oncogenesis Program The Wistar Institute Medical Research: What is the background for this study? What are the main findings? Response: Targeted therapies in cancer were hailed as a “magic bullet” because of their ability to act upon the mutations responsible for cancer while leaving nearby healthy cells alone. Using an approach like this, it would make sense that therapies designed to target mutations of BRAFV600E/K could be effective for melanoma, since that gene is mutated in about half of all cases of the disease. However, we’ve learned over time that these targeted therapies simply aren’t as effective as we had hoped they would be. In the case of these BRAF inhibitors, while patients do live slightly longer, they eventually relapse within months of treatment. We wanted to know why this was happening. We decided to look at macrophages, which are the most abundant inflammatory cells in melanoma. The more macrophages present in a patient with melanoma, the worse his or her outcome will be. They’ve been linked to cancer progression, but before this study, no one had really looked at the role they may play in the resistance to treatment with BRAF inhibitors. We found that BRAF inhibitors activate the mitogen-activated protein kinase (MAPK) pathway in macrophages. When this pathway is activated, it leads to the production of vascular endothelial growth factor (VEGF), a signaling protein closely associated with angiogenesis. The VEGF produced in the macrophages is able to activate the MAPK pathway in melanoma cells, thereby stimulating the growth of cancer cells. Taking these findings one step further, we discovered that when we blocked the MAPK pathway or VEGF signaling, we appeared to reverse macrophage-mediated resistance. When we targeted macrophages, we were able to increase the antitumor activity of BRAF inhibitors in mouse and human models. (more…)
Author Interviews, Genetic Research, Melanoma, Personalized Medicine / 08.03.2015

Pedram Gerami MD Associate Professor of Dermatology and Pathology Northwestern UniversityMedicalResearch.com Interview with: Pedram Gerami MD Associate Professor of Dermatology and Pathology Northwestern University MedicalResearch: What is the background for this study? What are the main findings? Dr. Gerami: The outcomes for patients with cutaneous melanoma are highly variable and there are limitations to the conventional staging system for melanoma. For example while the status of the sentinel lymph node biopsy is considered the strongest prognosticator, approximately 2/3 of cutaneous melanoma patients that ultimately die from their melanoma will have a negative sentinel lymph node biopsy result. In this study we showed that using a technique known as mRNA expression profiling to determine which genes are highly active and which are not that a molecular prognostic assay with accuracy could be developed. This assay can accurately classify patients based on their gene signature as having a high or low risk for metastasis and death from their melanoma. In an independent validation cohort, patients with a class I or low risk signature had a 5 year disease free survival rate of 97% while those with a class II or high risk signature had a 5 year disease free survival rate of only 31%. (more…)
Author Interviews, Dermatology, Melanoma / 06.03.2015

MedicalResearch.com Interview with: Alberto Pappo, M.D. Member, Oncology; Director, Solid Tumor Division St. Jude Children’s Research Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Pappo: Researchers have identified three distinct subtypes of childhood and adolescent tumors of pigment-producing skin cells called melanocytes. The subtypes have different genetic alterations and often different outcomes for patients. The findings should aid efforts to improve diagnosis and treatment of melanoma, which is the most common skin cancer in children and adolescents. The study provides the most comprehensive analysis yet of the genetic alteration underlying pediatric melanoma, including the first genetic evidence that sun damage causes melanoma in children and adolescents as well as adults. Researchers used whole genome sequencing and other techniques to study the normal and cancer genomes of 23 young patients with a variety of melanocytic tumors, including conventional melanoma. Patients ranged in age from 9 months to 19 years old. The melanoma subtypes in this study included conventional melanoma, which scientists showed was the same disease in children, adolescents and adults. More than 90 percent of pediatric conventional melanoma had DNA changes linked to sun damage. (more…)
Genetic Research, MD Anderson, Melanoma, Personalized Medicine / 04.03.2015

Linda Chin, MD Department Chair, Department of Genomic Medicine, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TXMedicalResearch.com Interview with: Linda Chin, MD Department Chair, Department of Genomic Medicine, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. Chin: BRAF inhibitors have worked very well against melanoma in the clinic, but when the tumors relapse on treatment, it is not always clear what causes it. Without this information, it can be difficult for doctors to identify specific second-line therapies likely to overcome the drug resistance. In this study, we used both mouse and patient melanoma samples to identify patterns of selected protein levels that can categorize modes of drug resistance when other assays such as DNA sequencing are uninformative. We hope that this information can provide missing clues for clinicians. (more…)
Author Interviews, Biomarkers, Melanoma, NYU, Personalized Medicine / 24.02.2015

Iman Osman, MD Professor, Departments of Dermatology, Medicine and Urology Associate Director, NYU Cancer Institute Director, Interdisciplinary Melanoma Program New York University Langone Medical Center New York, NY 10016MedicalResearch.com Interview with: Iman Osman, MD Professor, Departments of Dermatology, Medicine and Urology Associate Director The Laura and Isaac Perlmutter Cancer Center Director, Interdisciplinary Melanoma Program New York University Langone Medical Center New York, NY 10016 MedicalResearch: What is the background for this study? What are the main findings? Dr. Osman: We were interested in exploring molecules that could be biomarkers or functional regulators of metastasis in melanoma in early-stage tumor lesions on the skin. Though these tumors are treated largely the same (by surgical removal ), patients with these tumors have vastly different outcomes (apparent cure vs. metastatic spread of the disease). The reasons for these disparities are unclear and we have little ability to identify or predict the patients that will be cured and those that won’t. We also don’t have much data to know even if these tumors have differences at the molecular level. Our findings indicate that there are molecular differences in these tumors and that some of these differences contribute to tumor spread.  (more…)
Author Interviews, Melanoma, Yale / 22.02.2015

Douglas E. Brash, PhD Professor of Therapeutic Radiology and Dermatology Yale School of Medicine New Haven, CTMedicalResearch.com Interview with: Douglas E. Brash, PhD Professor of Therapeutic Radiology and Dermatology Yale School of Medicine New Haven, CT MedicalResearch: What is the background for this study? What are the main findings? Dr. Brash: We wanted to know whether the origin of melanoma differed from other cancers because of the melanin. It has long been known that blondes and redheads are sensitive to sunlight, but the prevailing view was that this was because their skin is light. But there are light-skinned, dark-haired people in countries near the equator and they don't have the high skin cancer incidence seen in Australia. Several labs, including ours, had irradiated cells or mice with UV and found more cell death in cells containing melanin than cells lacking melanin. In the last couple of years, two papers have focused attention on the issue; one study found that irradiating mice with UVA only gave melanomas if the skin contained melanin and the other study found that mice genetically predisposed to UV-induced melanoma developed melanomas even without UV if they also had red melanin. The most important findings are: First, our skin continues to be damaged by sunlight even when we're out of the sun. Second, the melanin pigment in your skin is bad for you as well as good: it may be carcinogenic as well as protective. Third, the chemistry underlying these events, chemical excitation of electrons, has not been seen in mammals before. (more…)
Author Interviews, Dermatology, JAMA, Melanoma / 17.02.2015

MedicalResearch.com Interview with: Caroline Watts| PhD Candidate Cancer Epidemiology and Services Research | Sydney School of Public Health The University of Sydney MedicalResearch: What is the background for this study? What are the main findings? Response: A clinic for people at high risk of melanoma was established at the Royal Prince Alfred Hospital, Sydney in 2006 to look at the impact of surveillance regime which included regular full body skin examination supported by dermoscopy and total body photography at 6 monthly intervals. If a suspicious lesion was identified, the lesion was either removed or sequential digital dermoscopy was performed and the patient returned in 3 months for review. This study aimed to estimate the costs associated with surveillance in this type of specilaised clinic. The mean number of clinic visits per year was 2.7 (95% CI, 2.5-2.8) for surveillance and 3.8 (95% CI, 3.4-4.1) for patients requiring surgical excisions. The mean annual cost per patient to the health system was A $882 (95% CI, A $783-$982) (US $599 [95% CI, US $532-$665]) and mean annual societal cost per patient (excluding health system costs) was A $972 (95% CI, A $899-$1045) (US $660 [95% CI, US $611-$710). Diagnosis of melanoma or non-melanoma skin cancer and frequent excisions for benign lesions in a relatively small number of patients was responsible for skewed health system costs. (more…)
Author Interviews, Genetic Research, Melanoma, Nature / 25.01.2015

MedicalResearch.com Interview with: Prof Lukas Sommer. Ph.D. Cell and Developmental Biology University of Zurich Institute of Anatomy Zurich Switzerland MedicalResearch: What is the background for this study? What are the main findings? Prof. Lukas Sommer:   Melanoma, the most aggressive of all skin cancers, is often fatal for patients due to the pronounced formation of metastases. Up to date, a melanoma’s rampant growth was mainly attributed to genetic causes, such as mutations in certain genes. However, we now reveal that so-called epigenetic factors also play a crucial role in the formation of metastases in malignant skin cancer. Epigenetic factors do not influence the gene sequence directly, but rather cause certain genes and chromosomal segments to be packed in different densities – and thus make them accessible for reading. In our study we identified “EZH2” as an epigenetic control protein found very frequently in malignant melanoma cells compared to normal cells. In these cells, “EZH2” controls genes that govern both tumor growth and genes that are important for the formation of metastases. We exploited this central position of EZH2 to combat the cancer by using a pharmacological inhibitor to suppress the activity of EZH2. As a result, we were able to prevent the growth and malignant spread of the cancer in an animal model and in human melanoma cells. (more…)
Author Interviews, Coffee, JNCI, Melanoma, NIH, Yale / 21.01.2015

MedicalResearch.com Interview with: Erikka Loftfield Doctoral student at the Yale School of Public Health Fellow at the National Cancer Institute Medical Research: What is the background for this study? What are the main findings? Response: Previous studies have reported conflicting results on the association between coffee drinking and melanoma. We sought to clarify this relationship using data from the large NIH-AARP Diet and Health Study. We followed over 400,000 retirees aged 50 to 71 years at study entry for an average of 10 years. Participants were asked to report typical coffee intake. During the course of follow-up nearly 3,000 cases of malignant melanoma occurred. In our study, we observed that individuals who reported the highest total coffee intake (4 cups/day) had about 20% lower risk of malignant melanoma compared with those who did not consume coffee. (more…)
Author Interviews, Melanoma / 14.01.2015

Keiran Smalley, PhD. Scientific Director, The Comprehensive Melanoma Research Center Associate Professor The Moffitt Cancer Center & Research Institute, Tampa, FLMedicalResearch.com Interview with: Keiran Smalley, PhD. Scientific Director, The Comprehensive Melanoma Research Center Associate Professor The Moffitt Cancer Center & Research Institute, Tampa, FL   Medical Research: What is the background for this study? What are the main findings? Dr. Smalley: Although many patients with BRAF mutant melanoma respond very well to BRAF inhibitors and the BRAF/MEK inhibitor combination, resistance is commonplace and the majority of those treated ultimately fail therapy. Most studies to date have focused upon the genetic changes that are associated with acquired BRAF and BRAF/MEK inhibitor resistance. We decided to take a different approach and to use proteomics to comprehensively map all of the signaling changes associated with resistance. Our study showed that melanoma cells with resistance to BRAF and BRAF/MEK inhibition were highly invasive and aggressive. This aggressive phenotype was driven through a cell surface receptor called EphA2, and this became upregulated in both melanoma cell cultures and in patient tumors following BRAF inhibitor treatment. As this suggested that the resistant cells would be more metastatic, we then performed animal experiments and analyzed tumors from melanoma patients receiving BRAF inhibitor. These studies showed an increase in EphA2 expression in the metastatic tumors that was lacking in the primary tumors. When we looked at cohorts of melanoma patients who received either a BRAF inhibitor or an older chemotherapy drug, we found that more of the BRAF inhibitor treated patients seemed to develop disease at new sites. Together this suggested that BRAF inhibition may switch the cancer cells to being more metastatic. (more…)
Author Interviews, Melanoma / 13.01.2015

MedicalResearch.com Interview with: Razieh Soltani-Arabshahi, MD, MSci Department of Dermatology, University of Utah, Salt Lake City, Utah MedicalResearch.com: What is the background for this study? Dr. Soltani-Arabshahi: The incidence of melanoma is rapidly rising. Dermatologists are the leading specialty group to diagnose melanoma. While ABCD cirteria for diagnosis of melanoma have been used by many dermatologists, there are few studies of it's predictive value. MedicalResearch.com: What are the main findings? Dr. Soltani-Arabshahi: We showed that at an academic dermatology center, nearly 16 clinically suspicious lesions need to be biopsied to find one case of melanoma. Biopsies of lesions larger than 6 mm in diameter on older male patients had the highest yield. (more…)
Author Interviews, Dermatology, Melanoma / 21.10.2014

Prof. David Whiteman Group leader, Cancer Control Group QIMR Berghofer Herston, QueenslandMedicalResearch.com Interview with: Prof. David Whiteman Group leader, Cancer Control Group QIMR Berghofer Herston, Queensland   Medical Research: What are the main findings of the study? Dr. Whiteman: Mortality from melanoma has continued to rise in Queensland, Australia, the jurisdiction with the world’s highest incidence of this disease. We analysed more than 4000 deaths from melanoma over the last 2 decades, and calculated mortality rates according the thickness of the primary lesion. (more…)
Author Interviews, Melanoma, Ophthalmology / 17.10.2014

MedicalResearch.com Interview with: Prof I. Jolanda M. de Vries Professor, Dept of Tumor Immunology Radboud University Nijmegen Medical Research: What are the main findings of the study? Prof. de Vries: Dendritic cells are antigen-presenting cells with the unique capacity to activate naive antigen-specific T cells, and by this means are very suitable to induce immunologic antitumor responses. Dendritic cells cultured from monocytes can be matured and loaded with tumor antigen ex vivo and administered back into the patient. Within the lymph node, dendritic cells present antigens to T cells to initiate an immune response. Metastatic uveal melanoma patients were vaccinated with autologous DCs loaded with tumor antigens (gp100 and tyrosinase), obtained by leukapheresis, according to a schedule of 3 biweekly vaccinations. One to 2 weeks after the last vaccination, a skin test was performed to analyse the induction of immunologic responses. We can conclude that dendritic cell vaccination is feasible and safe in metastatic uveal melanoma. Dendritic cell-based immunotherapy is potent to enhance the host’s antitumor immunity against uveal melanoma in approximately one third of patients. (more…)
Author Interviews, Melanoma, UCSF / 17.10.2014

Martina Sanlorenzo, MD Department of Dermatology Mt. Zion Cancer Research Bldg. San Francisco, CA 94143-0808MedicalResearch.com Interview with: Martina Sanlorenzo, MD Department of Dermatology Mt. Zion Cancer Research Bldg. San Francisco, CA 94143-0808 Medical Research: What are the main findings of the study? Dr. Sanlorenzo: In the treatment of BRAF mutant melanoma, the combination of BRAF inhibitor and MEK inhibitor has a better cutaneous safety profile compared with BRAF inhibitor monotherapy. Combination regimen shows fewer cutaneous adverse events and longer cutaneous adverse event-free interval. In particular, the development of squamous cell carcinoma or keratoacanthoma was significantly less frequent. (more…)
Author Interviews, Melanoma, PLoS / 16.10.2014

Professor Robert Insall CR-UK Beatson Institute for Cancer Research Glasgow UKMedicalResearch.com Interview with: Professor Robert Insall CR-UK Beatson Institute for Cancer Research Glasgow UK Medical Research: What are the main findings of the study? Prof. Insall: The principal message is that melanoma cells make their own steering signals, and thus drive themselves out of the tumour and into the bloodstream.  This comes in two parts: (a) The principal steering signal when we assay melanoma spread in vitro is lysophosphatidic acid, LPA.  LPA steers cells with really remarkable accuracy; blocking LPA receptors stops them from spreading without hurting their health or ability to move. (b) Where does the LPA gradient come from?  They make it themselves.  There seems to be lots of LPA around; they break down the LPA near them, leading to a gradient that's low near the cells and high further away.  This is the gradient that steers the tumour cells. (more…)
Author Interviews, Melanoma, NYU / 06.10.2014

David Polsky, MD, PhD Alfred W. Kopf, MD, professor of Dermatologic Oncology Ronald O. Perelman Department of Dermatology NYU Langone Medical CenterMedicalResearch.com Interview with: David Polsky, MD, PhD Alfred W. Kopf, MD, professor of Dermatologic Oncology Ronald O. Perelman Department of Dermatology NYU Langone Medical Center Medical Research: What are the main findings of the study? Dr. Polsky: We utilized a multi-disciplinary approach including an analysis of socioeconomic factors to elucidate the evolution of attitudes and behaviors maximizing personal ultraviolet light exposure during the 20th century in the United States.  We then compared melanoma incidence rates from national cancer registries to estimated skin exposure and found that they rose in parallel. Though causation cannot be made in an analysis such as this one, this paper describes a historical context for the changing attitudes promoting increased UV exposure, and the rising incidence of melanoma throughout the past century.  It also provides a framework in which to consider public health and education measures that may ultimately help reverse melanoma incidence trends. (more…)
Author Interviews, Melanoma, NEJM / 30.09.2014

Georgina Long BSc PhD MBBS FRACP Associate Professor of Melanoma Biology and Translational Research Melanoma Institute Australia and the University of Sydney MedicalResearch.com Interview with: Georgina Long BSc PhD MBBS FRACP Associate Professor of Melanoma Biology and Translational Research Melanoma Institute Australia and the University of Sydney Medical Research: Could you provide some background on this project? Why did you decide to do this research project? What prior work led up to this latest paper? Dr. Long: Pre-clinically, we had data that showed that the combination of BRAF inhibitor + MEK inhibitor
  • Decreased skin proliferative toxicity seen with BRAF inhibitors alone (seen as hyperproliferative lesions in rats)
  • and delayed the emergence of resistance I.e. The tumours in the mice reduced in size more, and stayed reduced for longer.We then confirmed this concept in a randomised phase 2 study, although it was not powered for a definitive progression free survival (PFS_ difference like a phase 3 trial is, we saw a strong difference in response rate and in PFS, yet there were only 54 patients per arm.
(more…)
Author Interviews, Melanoma / 21.09.2014

Mario Mandalà, MD Unit of Clinical Research Department of Oncology and Haematology Papa Giovanni XXIII Hospital Piazza OMS 1, 24100, Bergamo, ItalyMedicalResearch.com Interview with: Mario Mandalà, MD Unit of Clinical Research Department of Oncology and Haematology Papa Giovanni XXIII Hospital Piazza OMS 1, 24100, Bergamo, Italy Medical Research: What are the main findings of the study? Dr. Mandalà: We evaluated PD-L1 expression by IHC in 81 consecutive metastatic melanoma patients, with well-defined demographic and clinical characteristics. Protein expression levels were correlated with clinical outcome. PD-L1+ and PD-L1- subsets of the A375 cell line were stabilized in vitro and compared using gene expression profiling and functional assays. Results were confirmed using xenograft models. In our study PD-L1 membrane positivity was an independent negative prognostic marker. Furthermore PD-L1 expression defined a subset of the BRAF-mutated A375 cell line characterized by a highly invasive phenotype and by enhanced ability to grow in xenograft models. If confirmed, our clinical and experimental data suggest that PD-L1+ melanomas should be considered a disease subset with distinct genetic and morpho-phenotypic features, leading to enhanced aggressiveness and invasiveness. (more…)
Author Interviews, Cancer Research, Dartmouth, Melanoma, Nature / 12.09.2014

Dr. Constance Brinckerhoff Professor of Medicine Professor of Biochemistry Geisel School of Medicine at DartmouthMedicalResearch.com Interview with: Dr. Constance Brinckerhoff Professor of Medicine Professor of Biochemistry Geisel School of Medicine at Dartmouth Medical Research: What are the main findings of the study? Dr. Brinckerhoff: The genetic mutation BRAFV600E , frequently found in metastatic melanoma, not only secretes a protein that promotes the growth of melanoma tumor cells, but can also modify the network of normal cells around the tumor to support the disease’s progression. Targeting this mutation with Vemurafenib reduces this interaction, and suggests possible new treatment options for melanoma therapy. (more…)
Author Interviews, Melanoma / 01.08.2014

Marianne Berwick, PhD, MPH for the GEM Study Team Professor, Division of Epidemiology University of New Mexico, Department of Internal Medicine New Mexico Cancer Research Facility University of New Mexico, Albuquerque, NM 87131MedicalResearch.com Interview with: Marianne Berwick, PhD, MPH for the GEM Study Team Professor, Division of Epidemiology University of New Mexico, Department of Internal Medicine New Mexico Cancer Research Facility University of New Mexico, Albuquerque, NM 87131 Medical Research: What are the main findings of this study? Dr. Berwick: In our study of Sun Exposure and Melanoma Survival: A GEM Study we found that there is little strong evidence that sun exposure at any time in life influences melanoma-specific survival. This study took place in Australia, Italy, Canada and the United States among 3,578 individuals newly diagnosed with melanoma, who we followed for a mean of 7.4 years. (more…)
Author Interviews, Dermatology, Melanoma / 01.08.2014

MedicalResearch.com Interview with: Estee L. Williams, MD SUNY Downstate Medical Center, Brooklyn, New York Madfes Integrated Dermatology, New York, New York [email protected] Medical Research: What are the main findings of the study? Dr. Williams: In our retrospective review of all melanomas diagnosed at the Veterans’ Affairs Hospital in Brooklyn since 2000, we discovered that although a majority of the melanomas (63%) were found by the dermatologist during a yearly “full body” screening examination (versus detection by the patient), melanomas found by the dermatologist were not necessarily thinner (hence, earlier, more curable) than those found by the patient. (more…)
Author Interviews, Cancer Research / 16.07.2014

John D'Orazio, M.D., Ph.D. Drury Pediatric Research Endowed Chair Associate Professor, Univ. KY College of Medicine Pediatric Hematology-Oncology The Markey Cancer Center Lexington, KY 40536-0096MedicalResearch.com Interview with: John D'Orazio, M.D., Ph.D. Drury Pediatric Research Endowed Chair Associate Professor, Univ. KY College of Medicine Pediatric Hematology-Oncology The Markey Cancer Center Lexington, KY 40536-0096 Medical Research: What is the background for this study? Dr. D'Orazio: Malignant melanoma is the deadliest of skin cancers, and it’s incidence has increased enormously over the last several decades.  In the 1930’s only one in every fifteen hundred Americans would get melanoma in his/her lifetime.  Now it’s one in fifty or sixty.  Plus, it often affects young adults in the prime of their lives.  Altogether, nearly 10,000 Americans die of melanoma every year.  However, risk is not equally shared.  Fair-skinned people who tend to burn rather than tan from sun exposure have a much higher risk than dark skinned people.  On the surface, it would appear that the amount of melanin in the skin would be the only determinant of melanoma risk but the truth is more complex.  Our lab has been interested in a particular hormonal pathway in the skin that directly influences melanoma risk.  When UV radiation (sunlight) hits the skin, it causes damage to the cells of the skin.  Cells respond to this damage to protect themselves against further injury.  One way in which they do this is by turning on a hormone called melanocyte stimulating hormone, abbreviated “MSH”.  Made by keratinocytes, the most abundant cells in the epidermis, MSH is directly responsible for ramping up melanin production by melanocytes, the cells that make the pigment in the skin that gives us a tan.  This pigment called melanin acts as natural sunscreen and blocks UV radiation from penetrating into the skin.  This is very important because people who can tan are in a much safer state the next time they get sun exposure.  Because they have more melanin in the skin, the UV won’t cause as much damage.  The key is to realize that UV causes mutations in melanocytes, and with enough damage to the DNA, melanocytes can turn cancerous and become melanomas.   People who have the melanoma-prone, “can’t tan” skin type often have problems in this MSH hormonal pathway.  Specifically, they have inherited problems with the receptor on melanocytes that binds to MSH and makes the cells make more pigment.  This protein, called the melanocortin 1 receptor (or “MC1R”), is the way that melanocytes sense that the skin has been injured and needs more melanin.  If the MC1R won’t signal, then melanocytes just sit there and can’t be induced to make more melanin pigment.  Surely this is a major reason why people with MC1R signaling defects are at high risk of melanomas. (more…)
Author Interviews, Cancer Research / 20.06.2014

John L. VandeBerg PhD Southwest National Primate Research Center Texas Biomedical Research Institute San Antonio, TX 78245-0549MedicalResearch.com Interview with: John L. VandeBerg PhD Southwest National Primate Research Center Texas Biomedical Research Institute San Antonio, TX 78245-0549 MedicalResearch: What are the main findings of this study? Dr. VandeBerg: Despite the increasing use of sunscreen in recent decades, the incidence of melanoma continues to rise by 3% annually, leading to concerns that sunscreen may not be effective in preventing melanoma despite its efficacy in preventing sunburn.  Our results established in the laboratory opossum, which is the only natural mammalian model of UVB-induced melanoma, that SPF 15 sunscreen applied to infants prior to low dose UVB radiation leads later in life to a 10-fold reduction in pre-melanotic lesions, which are known to progress to malignant melanoma. (more…)
Melanoma, Sloan Kettering / 17.06.2014

Dr. Richard D. Carvajal MD Director, Developmental Therapeutics; Elizabeth and Felix Rohatyn Chair for Junior Faculty Memorial Sloan Kettering Cancer CenterMedicalResearch.com Interview with: Dr. Richard D. Carvajal MD Director, Developmental Therapeutics; Elizabeth and Felix Rohatyn Chair for Junior Faculty Memorial Sloan Kettering Cancer Center MedicalResearch: What are the main findings of the study? Dr. Carvajal: This is the first study to show that a systemic therapy provides significant clinical benefit in a randomized fashion to patients with advanced uveal melanoma, a population of patients who have very limited treatment options.   This clinical benefit has never previously been demonstrated with other agents, both conventional or investigational. (more…)
Author Interviews, Melanoma / 09.06.2014

Dr. Juliet A. Usher-Smith Clinical Lecturer in Primary Care The Primary Care Unit, University of Cambridge Strangeways Research Laboratory Cambridge, United Kingdom MedicalResearch.com Interview with: Dr. Juliet A. Usher-Smith Clinical Lecturer in Primary Care The Primary Care Unit, University of Cambridge Strangeways Research Laboratory Cambridge, United Kingdom MedicalResearch: What are the main findings of the study? Dr Usher-Smith: Our systematic review identified 25 risk models that have the potential to identify individuals at higher risk of developing melanoma. Comparison between the different models was difficult due to the lack of validation studies and heterogeneity in choice and definition of variables. We were, however, able to show that most include well established risk factors and that, despite including a range of different variables, there is very little heterogeneity in the discriminatory ability of the models. There was also little difference in model performance between those scores suitable for self-assessment and those requiring a health care professional, suggesting potential for use at a population level to identify people at higher risk of melanoma. (more…)