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Science (New York, N.Y.) Apr 2015Adoptive cell therapy (ACT) is a highly personalized cancer therapy that involves administration to the cancer-bearing host of immune cells with direct anticancer... (Review)
Review
Adoptive cell therapy (ACT) is a highly personalized cancer therapy that involves administration to the cancer-bearing host of immune cells with direct anticancer activity. ACT using naturally occurring tumor-reactive lymphocytes has mediated durable, complete regressions in patients with melanoma, probably by targeting somatic mutations exclusive to each cancer. These results have expanded the reach of ACT to the treatment of common epithelial cancers. In addition, the ability to genetically engineer lymphocytes to express conventional T cell receptors or chimeric antigen receptors has further extended the successful application of ACT for cancer treatment.
Topics: Antigens, Neoplasm; Genetic Engineering; Humans; Immunotherapy, Adoptive; Lymphocyte Depletion; Melanoma; Mutation; Neoplasms; Precision Medicine; Skin Neoplasms; T-Lymphocytes
PubMed: 25838374
DOI: 10.1126/science.aaa4967 -
Journal of the European Academy of... Jan 2022The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing. A growing part of this patient group is formed by immunocompromised patients, for... (Review)
Review
The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing. A growing part of this patient group is formed by immunocompromised patients, for example organ-transplant recipients (OTR). Although over 90% of the cSCC show a relatively harmless clinical behaviour, there is also a chance of developing advanced cSCC and metastases. Locally advanced cSCC are defined as cSCC that have locally advanced progression and are no longer amenable to surgery or radiation therapy. Better understanding of the clinical behaviour of cSCC is essential to discriminate between low- and high-risk cSCC. Staging systems are important and have recently been improved. Genetic characterisation of SCC will likely become an important tool to help distinguish low and high-risk cSCC with an increased potential to metastasise in the near future. Available treatments for high-risk and advanced cSCC include surgery, radiotherapy, chemotherapy and targeted therapy with epidermal growth factor receptors inhibitors. Anti-PD-1 antibodies show promising results with response rates of up to 50% in both locally advanced and metastatic cSCC but, in its present form, is not suitable for OTR.
Topics: Carcinoma, Squamous Cell; Humans; Immunocompromised Host; Neoplasm Staging; Skin Neoplasms
PubMed: 34855246
DOI: 10.1111/jdv.17728 -
Nature Reviews. Clinical Oncology Aug 2017Treatment options for patients with metastatic melanoma, and especially BRAF-mutant melanoma, have changed dramatically in the past 5 years, with the FDA approval of... (Review)
Review
Treatment options for patients with metastatic melanoma, and especially BRAF-mutant melanoma, have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents. During this period, the treatment paradigm for BRAF-mutant disease has evolved rapidly: the standard-of-care BRAF-targeted approach has shifted from single-agent BRAF inhibition to combination therapy with a BRAF and a MEK inhibitor. Concurrently, immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and, now, the programmed cell-death protein 1 (PD-1) immune checkpoints. These changes in the treatment landscape have dramatically improved patient outcomes, with the median overall survival of patients with advanced-stage melanoma increasing from approximately 9 months before 2011 to at least 2 years - and probably longer for those with BRAF-V600-mutant disease. Herein, we review the clinical trial data that established the standard-of-care treatment approaches for advanced-stage melanoma. Mechanisms of resistance and biomarkers of response to BRAF-targeted treatments and immunotherapies are discussed, and the contrasting clinical benefits and limitations of these therapies are explored. We summarize the state of the field and outline a rational approach to frontline-treatment selection for each individual patient with BRAF-mutant melanoma.
Topics: Humans; Immunotherapy; Melanoma; Molecular Targeted Therapy; Neoplasm Metastasis; Skin Neoplasms; Survival Analysis; Treatment Outcome
PubMed: 28374786
DOI: 10.1038/nrclinonc.2017.43 -
Expert Review of Anticancer Therapy Aug 2018The eighth edition of the American Joint Committee on Cancer (AJCC) melanoma staging system was implemented in the United States on 1 January 2018. Areas covered: This... (Review)
Review
The eighth edition of the American Joint Committee on Cancer (AJCC) melanoma staging system was implemented in the United States on 1 January 2018. Areas covered: This article provides an overview of important changes in the eighth edition AJCC staging system from the seventh edition based on analyses of a large international melanoma database. The clinical implications of these changes for melanoma treatment are also discussed. Expert commentary: A standardized and contemporary cancer staging system that facilitates accurate risk stratification is essential to guide patient treatment. The eighth edition of the AJCC staging system is currently the most widely accepted approach to melanoma staging and classification at initial diagnosis.
Topics: Databases, Factual; Humans; Melanoma; Neoplasm Staging; Risk Assessment; Skin Neoplasms; United States
PubMed: 29923435
DOI: 10.1080/14737140.2018.1489246 -
Modern Pathology : An Official Journal... Feb 2016Plasmacytoid dendritic cell neoplasms manifest in two clinically and pathologically distinct forms. The first variant is represented by nodular aggregates of clonally... (Review)
Review
Plasmacytoid dendritic cell neoplasms manifest in two clinically and pathologically distinct forms. The first variant is represented by nodular aggregates of clonally expanded plasmacytoid dendritic cells found in lymph nodes, skin, and bone marrow ('Mature plasmacytoid dendritic cells proliferation associated with myeloid neoplasms'). This entity is rare, although likely underestimated in incidence, and affects predominantly males. Almost invariably, it is associated with a myeloid neoplasm such as chronic myelomonocytic leukemia or other myeloid proliferations with monocytic differentiation. The concurrent myeloid neoplasm dominates the clinical pictures and guides treatment. The prognosis is usually dismal, but reflects the evolution of the associated myeloid leukemia rather than progressive expansion of plasmacytoid dendritic cells. A second form of plasmacytoid dendritic cells tumor has been recently reported and described as 'blastic plasmacytoid dendritic cell neoplasm'. In this tumor, which is characterized by a distinctive cutaneous and bone marrow tropism, proliferating cells derive from immediate CD4(+)CD56(+) precursors of plasmacytoid dendritic cells. The diagnosis of this form can be easily accomplished by immunohistochemistry, using a panel of plasmacytoid dendritic cells markers. The clinical course of blastic plasmacytoid dendritic cell neoplasm is characterized by a rapid progression to systemic disease via hematogenous dissemination. The genomic landscape of this entity is currently under intense investigation. Recurrent somatic mutations have been uncovered in different genes, a finding that may open important perspectives for precision medicine also for this rare, but highly aggressive leukemia.
Topics: Biomarkers, Tumor; Biopsy; Cell Differentiation; Cell Lineage; Cell Proliferation; Dendritic Cells; Genetic Predisposition to Disease; Hematologic Neoplasms; Humans; Immunohistochemistry; Immunophenotyping; Mutation; Phenotype; Predictive Value of Tests; Prognosis; Skin Neoplasms
PubMed: 26743477
DOI: 10.1038/modpathol.2015.145 -
Mini Reviews in Medicinal Chemistry 2016Melanoma claims approximately 80% of skin cancer-related deaths. Its life-threatening nature is primarily due to a propensity to metastasize. The prognosis for melanoma... (Review)
Review
Melanoma claims approximately 80% of skin cancer-related deaths. Its life-threatening nature is primarily due to a propensity to metastasize. The prognosis for melanoma patients with distal metastasis is bleak, with median survival of six months even with the latest available treatments. The most commonly mutated oncogenes in melanoma are BRAF and NRAS accounting approximately 60% and 20% of cases, respectively. In malignant melanoma, accumulating evidence suggests that multiple signaling pathways are constitutively activated and play an important role in cell proliferation, cell survival, epithelial to mesenchymal transition, metastasis and resistance to therapeutic regimens. Phytochemicals are gaining considerable attention because of their low toxicity, low cost, and public acceptance as dietary supplements. Cell culture and animals studies have elucidated several cellular and molecular mechanisms by which phytochemicals act in the prevention and treatment of metastatic melanoma. Several promising phytochemicals, such as, fisetin, epigallocatechin-3-gallate, resveratrol, curcumin, proanthocyanidins, silymarin, apigenin, capsaicin, genistein, indole-3-carbinol, and luteolin are gaining considerable attention and found in a variety of fresh fruits, vegetables, roots, and herbs. In this review, we will discuss the preventive potential, therapeutic effects, bioavailability and structure activity relationship of these selected phytochemicals for the management of melanoma.
Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Proliferation; Humans; Melanoma; Mutation; Neoplasm Invasiveness; Phytochemicals; Signal Transduction; Skin; Skin Neoplasms
PubMed: 26864554
DOI: 10.2174/1389557516666160211120157 -
Ugeskrift For Laeger Jul 2018Muir-Torre syndrome (MTS) is an autosomal dominant disease with approximately 200 reported cases worldwide, which is characterised by multiple neoplasms of the skin and...
Muir-Torre syndrome (MTS) is an autosomal dominant disease with approximately 200 reported cases worldwide, which is characterised by multiple neoplasms of the skin and internal organs. This is a case report of a 57-year-old woman with MTS, who was referred to a plastic surgery department from a gastroenterology department due to a neoplasm of the skin. After treatment, she was referred to a dermatology department for follow-up. MTS is a rare disease, which is now reported in Denmark. Doctors treating any of the composing elements should have basic knowledge of the condition in order to refer patients appropriately.
Topics: Female; Humans; Middle Aged; Muir-Torre Syndrome; MutS Homolog 2 Protein; Mutation; Skin Neoplasms
PubMed: 29984696
DOI: No ID Found -
Neoplasia (New York, N.Y.) Sep 2023Cutaneous melanoma is the deadliest form of skin neoplasm and its high mortality rates could be averted by early accurate detection. While the detection of melanoma is...
Cutaneous melanoma is the deadliest form of skin neoplasm and its high mortality rates could be averted by early accurate detection. While the detection of melanoma is currently reliant upon melanin visualisation, research into melanosome biogenesis, as a key driver of pathogenesis, has not yielded technology that can reliably distinguish between atypical benign, amelanotic and melanotic lesions. The endosomal-lysosomal system has important regulatory roles in cancer cell biology, including a specific functional role in melanosome biogenesis. Herein, the involvement of the endosomal-lysosomal system in melanoma was examined by pooled secondary analysis of existing gene expression datasets. A set of differentially expressed endosomal-lysosomal genes was identified in melanoma, which were interconnected by biological function. To illustrate the protein expression of the dysregulated genes, immunohistochemistry was performed on samples from patients with cutaneous melanoma to reveal candidate markers. This study demonstrated the dysregulation of Syntenin-1, Sortilin and Rab25 may provide a differentiating feature between cutaneous melanoma and squamous cell carcinoma, while IGF2R may indicate malignant propensity in these skin cancers.
Topics: Humans; Melanoma; Skin Neoplasms; Carcinoma, Squamous Cell; Lysosomes; rab GTP-Binding Proteins; Melanoma, Cutaneous Malignant
PubMed: 37562257
DOI: 10.1016/j.neo.2023.100924 -
Cells Aug 2021Cutaneous melanoma is a lethal disease, even when diagnosed in advanced stages. Although recent progress in biology and treatment has dramatically improved survival... (Review)
Review
Cutaneous melanoma is a lethal disease, even when diagnosed in advanced stages. Although recent progress in biology and treatment has dramatically improved survival rates, new therapeutic approaches are still needed. Deregulation of epigenetics, which mainly controls DNA methylation status and chromatin remodeling, is implied not only in cancer initiation and progression, but also in resistance to antitumor drugs. Epigenetics in melanoma has been studied recently in both melanoma preclinical models and patient samples, highlighting its potential role in different phases of melanomagenesis, as well as in resistance to approved drugs such as immune checkpoint inhibitors and MAPK inhibitors. This review summarizes what is currently known about epigenetics in melanoma and dwells on the recognized and potential new targets for testing epigenetic drugs, alone or together with other agents, in advanced melanoma patients.
Topics: Antineoplastic Agents; Chromatin Assembly and Disassembly; DNA Methylation; Drug Resistance, Neoplasm; Epigenesis, Genetic; Humans; Melanoma; RNA, Untranslated; Skin Neoplasms
PubMed: 34440824
DOI: 10.3390/cells10082048 -
The FEBS Journal Jul 2017Melanoma is a skin cancer notorious for its metastatic potential. As an initial step of the metastatic cascade, melanoma cells part from the primary tumour and invade... (Review)
Review
Melanoma is a skin cancer notorious for its metastatic potential. As an initial step of the metastatic cascade, melanoma cells part from the primary tumour and invade the surrounding tissue, which is crucial for their dissemination and the formation of distant secondary tumours. Over the last two decades, our understanding of both, general and melanoma specific mechanisms of invasion has significantly improved, but to date no efficient therapeutic strategy tackling the invasive properties of melanoma cells has reached the clinic. In this review, we assess the major contributions towards the understanding of the molecular biology of melanoma cell invasion with a focus on melanoma specific traits. These traits are based on the neural crest origin of melanoma cells and explain their intrinsic invasive nature. A particular emphasis is given not only to lineage specific signalling mediated by TGFβ, and noncanonical and canonical WNT signalling, but also to the role of PDE5A and RHO-GTPases in modulating modes of melanoma cell invasion. We discuss existing caveats in the current understanding of the metastatic properties of melanoma cells, as well as the relevance of the 'phenotype switch' model and 'co-operativity' between different phenotypes in heterogeneous tumours. At the centre of these phenotypes is the lineage commitment factor microphthalmia-associated transcription factor, one of the most crucial regulators of the balance between de-differentiation (neural crest specific gene expression) and differentiation (melanocyte specific gene expression) that defines invasive and noninvasive melanoma cell phenotypes. Finally, we provide insight into the current evidence linking resistance to targeted therapies to invasive properties of melanoma cells.
Topics: Animals; Antineoplastic Agents; Cell Differentiation; Gene Expression Regulation, Neoplastic; Humans; Melanoma; Molecular Targeted Therapy; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Phenotype; Signal Transduction; Skin Neoplasms
PubMed: 28196297
DOI: 10.1111/febs.14040