Diabetes Drug Reverses Aging Medium That Promotes Melanoma

MedicalResearch.com Interview with:

Reeti Behera, Ph.D. Postdoctoral fellow in the Weeraratna lab The Wistar Institute Philadelphia PA

Dr. Behera

Reeti Behera, Ph.D.
Postdoctoral fellow in the Weeraratna lab
The Wistar Institute
Philadelphia PA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Malignant melanoma is an aggressive disease and is the cause of the majority of skin cancer deaths. In particular, older individuals have a much poorer prognosis for melanoma and are more resistant to targeted therapy than compared to young individuals. A recently published study from our lab has shown that age-related changes in secreted factors in the microenvironment can drive melanoma progression and therapy resistance.

Klotho is a protein whose expression levels decreases with aging. In this study, we have shown that a decrease in klotho levels in the aged microenvironment drives melanoma aggression and therapy resistance by promoting the oncogenic signaling pathway Wnt5A. We also have shown that reconstituting klotho levels in the aged microenvironment by using rosiglitazone, an FDA-approved drug used to treat diabetes, can reduce tumor burden in aged mice. We also show that Klotho expression is decreased in therapy-resistant melanoma tumors. Reconstituting klotho levels in therapy-resistant melanoma cells by treating with rosiglitazone can inhibit Wnt5A levels and MAPK pathway. We also show that rosiglitazone can significantly decrease therapy-resistant tumor burden in the aged mice, but not in the young.

Continue reading

Diabetes Drug May Enhance Melanoma Chemotherapy

MedicalResearch.com Interview with:

Bin Zheng, PhD Assistant Professor Cutaneous Biology Research Center Massachusetts General Hospital Harvard Medical School Charlestown, MA 02129

Dr. Bin Zheng

Bin Zheng, PhD
Assistant Professor
Cutaneous Biology Research Center
Massachusetts General Hospital
Harvard Medical School
Charlestown, MA 02129 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Melanoma is the most deadly form of skin cancer with more than 75,000 newly diagnosed cases in the US each year. Over the years, various genetic driver mutations have been identified that cause melanoma, including mutations in the genes BRAF and NRAS. Recent genetic insights into the development of melanoma showed that also mutations in NF1 can lead to melanoma. While there are targeted therapies available for BRAF-mutant melanoma, thus far no such therapies are available for NF1-mutant melanoma. We identified that using a combination of an ERK inhibitor, SCH772984, and the antidiabetic drug phenformin could provide a novel therapeutic strategy for NF1-mutatnt melanomas.

Continue reading

Regional and State Differences in Melanoma Rates in the US

MedicalResearch.com Interview with:
Jessica S. Mounessa, BS
Robert P. Dellavalle, MD, PhD, MSPH
Dermatology Service, Denver Veterans Affairs Medical Center, Denver, Colorado
Department of Dermatology, University of Colorado School of Medicine, Aurora

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Skin cancer remains the most common cancer in the U.S., despite ongoing efforts to address this major public health problem. Over 9,000 deaths occur annually, and mortality rates continue to increase faster than those associated with any other preventable cancer. Malignant melanoma, the deadliest type of skin cancer, accounts for the overwhelming majority of these deaths.

Our study identified regional and state differences in the incidence and mortality rates of melanoma in the United States. We found that the Northeast, specifically New England, represents the only U.S. region in which the majority of states experienced a reduction in both incidence and death rates over the ten-year period between 2003 and 2013.

Continue reading

Is Skin Cancer Screening Cost Effective?

MedicalResearch.com Interview with:
Isabelle Hoorens, MD, PhD

Department of Dermatology
Ghent University Hospital
Ghent, Belgium

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In this study we questioned whether a population-based screening for skin cancer is cost-effective.

In addition we compared the cost-effectiveness of two specific screening techniques. The first technique, a lesion-directed screening being a free-of-charge skin cancer check of a specific lesion meeting 1 or more of the following criteria: ABCD rule (asymmetry, border irregularity, color variation, and diameter >6 mm), “ugly duckling” sign, new lesion lasting longer than 4 weeks, or red nonhealing lesions.

The second screening technique consisted of a systematic total body examination in asymptomatic patients. A clinical screening study was performed in Belgium in 2014. Continue reading

Pembrolizumab Found to Be Cost-Effective in Advanced Melanoma

MedicalResearch.com Interview with:

Herbert H F Loong MBBS(HK), PDipMDPath(HK), MRCP(UK), FHKCP, FHKAM(Medicine) Specialist in Medical Oncology Clinical Assistant Professor, Department of Clinical Oncology Deputy Medical Director, Phase 1 Clinical Trials Centre The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong SAR

Dr. Herbert Loong

Herbert H F Loong
MBBS(HK), PDipMDPath(HK), MRCP(UK), FHKCP, FHKAM(Medicine)
Specialist in Medical Oncology
Clinical Assistant Professor, Department of Clinical Oncology
Deputy Medical Director, Phase 1 Clinical Trials Centre
The Chinese University of Hong Kong
Prince of Wales Hospital
Hong Kong SAR

MedicalResearch.com: What is the background for this study? 

Response: Advanced melanoma have previously been known to be a disease with a dismal prognosis. Over the last few years, clinical trials data and real-world clinical experience of checkpoint inhibitors have significantly changed the treatment landscape for advanced melanoma patients. This was first demonstrated with the Anti-CTLA4 Ab Ipilimumab, and more recently with the Anti-PD1 Ab pembrolizumab. Whilst we have seen dramatic improvements in disease control with the use of these agents, the high costs of these drugs may be prohibitive to the average patient who has to pay out-of-pocket and potentially may place significant burdens on healthcare systems. There is a need to rationally assess the cost-effectiveness of these new agents, specifically addressing the potential benefits to the individual patient and to society, whilst balancing the costs that such a treatment may entail.

The assessment of cost-effectiveness of a particular treatment is extremely important in Hong Kong, as this has direct implications on drug reimbursement and accessibility of the particular drug in question at public hospitals in Hong Kong. The aim of the study is to assess the cost-effectiveness of pembrolizumab in patients with advanced melanoma used in the first-line setting in Hong Kong, and comparing it to (1) ipilimumab and (2) cytotoxic chemotherapy. Cytotoxic chemotherapy chosen for comparison were drugs commonly used in the first line setting in Hong Kong, which included dacarbazine, temozolomide and carboplatin+paclitaxel combination. It is important to note that whilst ipilimumab is registered for this indication in Hong Kong, there is no reimbursement of this drug by the Hospital Authority in Hong Kong and patients have to pay out-of-pocket. The cost of ipilimumab and the associated side effects has been prohibitive to most advanced melanoma patients in the public setting.

Continue reading

Patients and Partners Not Embarrassed To Do Skin Cancer Examinations On Each Other

MedicalResearch.com Interview with:

June K. Robinson, MD Research Professor of Dermatology Northwestern University Feinberg School of Medicine Department of Dermatology Chicago, IL 60611

Dr. June Robinson

June K. Robinson, MD
Research Professor of Dermatology
Northwestern University Feinberg School of Medicine
Department of Dermatology
Chicago, IL 60611

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This is a secondary finding from a randomized controlled trial of a structured skills training program for melanoma patients and their skin check partners.

The pairs learned and performed skin self-examination for the early detection of melanoma. They continued to perform skin checks for 2 years and trained pairs identified more early melanoma (melanoma in situ and Stage 1A melanoma) than controls.

Continue reading

Thin Melanomas Have Surprisingly High Mortality Risk

MedicalResearch.com Interview with:

Shoshana M. Landow, MD, MPH FAAD Dermatoepidemiology Unit Providence Veterans Affairs Medical Center Providence, RI 02908.

Dr. Shoshana M. Landow

Shoshana M. Landow, MD, MPH FAAD
Dermatoepidemiology Unit
Providence Veterans Affairs Medical Center
Providence, RI 02908.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Interest for this study arose from a realization that a large number of deaths from thin melanomas have been documented in SEER. Since prognosis worsens with depth for thicker melanomas, we sought to evaluate whether it was the “thicker” of the thin melanomas that accounted for most of the deaths. We were surprised to find that when we restricted our study to melanomas diagnosed at Stage I and II, the greatest number of deaths at 10 years caused by these melanomas resulted from those 1.00mm and less in depth. We were also surprised to find that prognosis for ultra-thin melanomas, 0.01-0.25mm in depth, was not better than those 0.26-0.50mm, as we had expected.

Continue reading

PD-1 Blockers Improve Survival in Melanoma, With Lowest Risk of Side Effects

MedicalResearch.com Interview with:

Feng Xie, Ph.D.</strong> Associate Professor Department of Clinical Epidemiology and Biostatistics Faculty of Health Sciences, McMaster University

Dr. Feng Xie

Feng Xie, Ph.D.
Associate Professor
Department of Clinical Epidemiology and Biostatistics
Faculty of Health Sciences
McMaster University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cutaneous melanoma, an aggressive and deadly form of skin cancer, in early stages is often cured with surgery alone. Most patients presenting with advanced-stage disease, however, are not candidates for surgery and drug therapy is the main course of treatment. Around 40-60% of melanomas have a mutation in the BRAF protein. Multiple effective first-line treatment options are available for patients with advanced BRAF-mutated melanoma, which fall under two established classes of drug therapies: targeted therapy and immunotherapy. Presently, it remains uncertain which is the optimal first-line treatment.

In our network meta-analysis we evaluated 15 randomized controlled trials published between 2011 and 2015 assessing the benefits and harms of targeted or immune checkpoint inhibitors in 6662 treatment naïve patients with lymph node metastasis not amenable to surgery or distant metastatic melanoma.

We found that combined BRAF and MEK targeted therapy and PD-1 immunotherapy were both equally effective in improving overall survival. Combined BRAF and MEK inhibition was most effective in improving progression-free survival. PD-1 inhibition was associated with the lowest risk of serious adverse events.

Continue reading

Mitotic Rate Correlates With Sentinel Lymph Node Status and Outcome in Cutaneous Melanoma

MedicalResearch.com Interview with:
Dr. Mario Mandalà, MD

Division of Oncology, Department of Oncology and Hematology
Papa Giovanni XXIII Hospital
Bergamo, Italy. 

MedicalResearch.com: What is the background for this study?

Response: The 7th edition of the TNM AJCC classification incorporated mitotic rate (MR) only for primary cutaneous melanoma with Breslow thickness ≤1 mm. We investigated whether and to what extent MR is able to predict sentinel lymph node (SLN) status and clinical outcome of  primary cutaneous melanoma (PCM) patients with BT >1 mm.

Continue reading

Do Dysplastic Moles Need To Be Re-Excised?

MedicalResearch.com Interview with:
Timothy Patton, DO

Department of Dermatology
Falk Medical Center
University of Pittsburgh Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: As dermatologists we are confronted daily with how to manage lesions that are biopsied and diagnosed as dysplastic nevi. These lesions are considered by some to be potential melanoma precursors and by others as benign lesions with little to no malignant potential. Often, particularly for lesions with severe atypia these lesions are re excised. There are no prospective studies or consistent guidelines as to how to manage these lesions. We decided to retrospectively look at the outcome of 451 patients with dysplastic nevi with severe atypia, many of whom had not had their lesions re-excised, who had at least 5 years of follow up to determine if any developed melanoma at the site of the biopsied dysplastic nevus or distantly. We found no cases of metastatic melanoma in patients who did not already have a diagnosis of melanoma. We found two cases of thin melanoma in patients who had their lesions re-excised. Both of those patients were treated with reexcision and did not develop subsequent melanoma metastasis or recurrence. Continue reading