Melanoma Research

Checkpoint blockade immunotherapy has revolutionized the treatment of advanced melanoma, with impressive survival benefits attained through upregulation of the anticancer immune response. Blockade of regulatory checkpoint molecules can, however, also result in aberrant immune activation leading to undesirable inflammation and autoimmunity. Although many genetic determinants have been described in patients with primary autoimmune diseases, it is uncertain whether patients developing autoimmune skin disease as an adverse effect of anti-PD-1 therapy share the same genetic risks...

The development of immunotherapy has improved the treatment of melanoma; however, resistance and frequent recurrence persist and remain a major problem. N-methyladenosine (mA) is the most abundant epitranscriptomic mark on mRNA and is essential for various physiological processes; however, its role in melanoma is unknown. Utilizing human normal melanocyte and melanoma cell lines, we analyzed the expression of METTL3 by quantitative RT-PCR. We inhibited the METTL3 expression by shRNA and analyzed the effects on melanoma cell proliferation, colony formation ability, and invasion...

Selective inhibition of the mutant BRAF protein is a highly promising therapeutic approach for melanoma patients carrying the BRAF mutation. Despite the remarkable clinical response, most patients develop resistance and experience tumour regrowth. To clarify the molecular background of BRAF inhibitor resistance, we generated four drug-resistant melanoma cell lines from paired primary/metastatic cell lines using a vemurafenib analogue PLX4720. Three of the resistant cell lines showed decreased proliferation after drug withdrawal, but the proliferation of one cell line (WM278) increased notably...

Iris melanoma is a rare tumour that accounts for ∼3-4% of all uveal melanoma cases. In the past, surgical resection was the sole treatement option, whereas nowadays, it has been replaced by brachytherapy as treatment of choice. Surgical resection is still in use in selected cases but combined with adjuvant radiotherapy in cases of incomplete resection. Herein, we report the case of a very late recurrence, 45 years after surgical resection. A literature review was performed to detect the latest recurrence reported to date and to understand the etiology behind very late recurrences...

Although T-cell checkpoint blockade has revolutionized melanoma therapy, metastatic melanoma in pregnancy remains a challenging area of unmet need. Treatment with anti-PD1 therapy decreases foetal-maternal tolerance and increases the risk of pregnancy loss in animal studies and is considered category D by the Food and Drug Administration. We describe a unique case of conception and pregnancy, with successful maternal and foetal outcomes, in a patient with metastatic melanoma who had received combination anti-CTLA-4 and anti-PD1 therapy...

Advanced melanoma (AM) represents the leading cause of death from skin cancer. To date, the crucial role of the immune system in AM pathogenesis and progression is well known, but the prognostic value of clinicopathological characteristics remains unclear. Lactate dehydrogenase (LDH) is an ascertained prognostic indicator and previous data showed that AM patients treated with BRAF and MEK inhibitors with normal LDH values and fewer than three metastatic sites achieved a better outcome. Moreover, the neutrophil-to-lymphocytes ratio and the lymphocyte-to-monocyte ratio (LMR) have been suggested as other potential prognostic factors...

OBJECTIVE: New melanoma therapies have shifted the expectations of patients and providers. Evaluating the impact of treatment characteristics may enhance shared decision making. PATIENTS AND METHODS: A survey, including a discrete choice experiment, was utilized to evaluate perceived trade-offs of different melanoma treatments and to estimate out-of-pocket (OOP) willingness-to-pay (WTP) thresholds (January 2016 to March 2016). Participants included patients with melanoma at Huntsman Cancer Institute and their cancer care providers...

The rising incidence of cutaneous melanoma (CM), an aggressive skin cancer, emphasizes the need for novel biomarkers to guide personalized care and better predict outcome. Genetic factors including germline risk variants are promising candidates for this aim. We explored the association between germline risk variants and melanoma outcome in a large genetically homogenous Belgian melanoma population, focusing on single nucleotide polymorphisms which generated the highest association with melanoma susceptibility...

Cutaneous amelanotic melanoma (AM) is a rare amelanotic or a hypomelanotic subtype of melanoma, comprising only 0.4-27.5% of all melanoma cases. The mean age of the patients is over 50 years, and the male/female ratio varies from 0.5 to 4. Patients with red hair, type I skin, freckles, lack of nevi on the back, a sun-sensitive phenotype, or previous AM history are more likely to develop AMs. As AMs lack pigmentation, their appearances vary and can mimic many benign and malignant conditions, thus presenting a diagnostic challenge...

OBJECTIVE: The overall survival (OS) of patients with metastatic uveal melanoma is short, the evidence for effectiveness of treatments is limited, and no consensus on the choice of treatment exists. We aimed to advance interpretation of OS as an outcome by pooling peer-reviewed data. PATIENTS AND METHODS: The design is a systematic review and meta-analysis. We searched PubMed from 1 January 1980, to 29 March 2017, for articles reporting patient-level survival in Kaplan-Meier or numerical form...

Uveal melanoma (UM), the most common primary intraocular tumour, is often complicated by exudative retinal detachment (RD). Sometimes, this exudative RD is mistaken for a rhegmatogenous detachment and is subsequently treated with vitrectomy with silicone oil (SiOil) tamponade. As SiOil prevents ultrasound imaging, the diagnosis, treatment planning and/or follow-up of UM underlying the detachment are often severely hindered by the SiOil. We aim to develop and evaluate new MRI methods to image UM patients with a SiOil tamponade and evaluate this in vivo...

Long noncoding RNA X-inactive specific transcript (XIST) was confirmed to participate in the development of many cancers. However, the function of XIST in malignant melanoma (MM) remained largely unknown. In the current study, we found that the XIST expression level was upregulated in MM tissues and cell lines. In addition, the growth rate of MM cells transfected with silencing XIST was significantly decreased compared with that with silencing normal control. XIST knockdown inhibited proliferation and migration in MM cells and increased the oxaliplatin sensitivity of oxaliplatin-resistant MM cells...

Inositol hexaphosphate (IP6) also called phytic acid is a polyphosphorylated carbohydrate naturally found in cereals, nuts, grains, and high-fiber-containing foods. It has been shown to inhibit the growth of many different tumor cell lines both in vitro and in vivo like colon, pancreas, liver, prostate, and even melanoma. Vitamin B inositol is a precursor of IP6 and another naturally occurring compound with anticancer properties. We present a case report of a patient with metastatic melanoma who declined traditional therapy and opted to try over the counter supplement IP6+inositol instead...

Until now, malignancy has been considered a cellular problem represented by the perturbed (uncontrolled) division of the cells associated with invasion and metastasis. Contrary to this classical approach, a new perspective suggests that cancerous disease is, in fact, a supracellular problem represented by inadequate evolution of complex supracellular processes (embryogenesis, development, regeneration, etc.). Such complex processes would be disconnected from the real needs of the body, inducing unnecessary or even dangerous events such as an exacerbated rate of the cell division, angiogenesis, immunosuppression (specific to embryogenesis and melanoma), invasion (mediated by trophoblastic/placental factors in melanoma), and migration (specific to neural crest cells, which generate melanocytes - the most common origin for melanoma)...

The cancer/testis antigen (CTA) family is a group of antigens whose expression is restricted to male germline cells of the testis and various malignancies. This expression pattern makes this group of antigens potential targets for immunotherapy. The aim of this study was to create an overview of CTA expressed by melanoma cells at mRNA and protein level. A systematic literature search was performed in Medline (PubMed) and Embase from inception up to and including February 2018. Studies were screened for eligibility by two independent reviewers...

After a long-term increase, the incidence of cutaneous malignant melanoma has stabilized recently or even decreased in several populations of North-western Europe, USA, Canada, Australia and New Zealand, but not in southern Europe. The incidence trends of primary invasive cutaneous malignant melanoma (International Classification of Diseases, 10th revision, codes C43.0-C43.9) in the Romagna Region (northern Italy, 1.2 million inhabitants) for the period 1986-2014 were analysed with an age-period-cohort modelling approach...

This retrospective cohort study assessed the prognostic significance of distant metastasis-free interval (DMFI) in patients with relapsed BRAF-mutant melanoma treated with BRAF with or without MEK inhibitors (BRAFi±MEKi). Patients with a DMFI of up to 24 months were compared with those with DMFI of more than 24 months, with regard to their postrelapse progression-free survival (PR-PFS) and overall survival (PR-OS). In total, 109 patients were included in the study. Median DMFI was 25.3 (range: 3.4-188.2) months...

In several cancers, tumor progression is associated with the infiltration of tumor-associated macrophages (TAMs). The aim was to evaluate the prognostic significance of expression of CD163 and CD68 (TAMs' markers) and their correlation with vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) expression in cutaneous melanoma. Diagnostic tissues from 102 patients of cutaneous melanoma were evaluated by immunohistochemistry for their CD68, CD163, VEGF, and COX-2 expression. Correlations between the proteins were then investigated...

Current evidences suggest that mast cells contribute to the proliferation and differentiation of skin melanocytes. According to these findings, we carried out an observational cross-sectional study to investigate the correlation between the total number of nevi (TN), Breslow thickness (BT), and serum tryptase (ST) levels in a cohort of 35 melanoma (MM) patients. A Mann-Whitney test was performed to compare ST values within each variable. Subsequently, the independent predictive factors were assessed by multiple logistic regression...

The gut microbiota impacts response to immunotherapy in cancer patients. We sought to evaluate the role of physiologic colonic fluorine-18-fluorodeoxyglucose (F-FDG) uptake, a test that was recently shown to reflect colonic bacterial load, as a possible predictor for response to immunotherapy. We carried out a retrospective study in metastatic melanoma patients who received the immune checkpoint inhibitor ipilimumab as first-line therapy. All patients underwent an F-FDG PET scan before treatment initiation...