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      Current state of melanoma diagnosis and treatment

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          ABSTRACT

          Melanoma is the deadliest form of skin cancer. In the early stages, melanoma can be treated successfully with surgery alone and survival rates are high, but after metastasis survival rates drop significantly. Therefore, early and correct diagnosis is key for ensuring patients have the best possible prognosis. Melanoma misdiagnosis accounts for more pathology and dermatology malpractice claims than any cancer other than breast cancer, as an early misdiagnosis can significantly reduce a patient’s chances of survival. As far as treatment for metastatic melanoma goes, there have been several new drugs developed over the last 10 years that have greatly improved the prognosis of patients with metastatic melanoma, however, a majority of patients do not show a lasting response to these treatments. Thus, new biomarkers and drug targets are needed to improve the accuracy of melanoma diagnosis and treatment. This article will discuss the major advancements of melanoma diagnosis and treatment from antiquity to the present day.

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          Immune checkpoint blockade: a common denominator approach to cancer therapy.

          Suzanne Topalian, Charles Drake, Drew M Pardoll (2015)
          The immune system recognizes and is poised to eliminate cancer but is held in check by inhibitory receptors and ligands. These immune checkpoint pathways, which normally maintain self-tolerance and limit collateral tissue damage during anti-microbial immune responses, can be co-opted by cancer to evade immune destruction. Drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD-1, anti-PD-L1, and others in early development, can unleash anti-tumor immunity and mediate durable cancer regressions. The complex biology of immune checkpoint pathways still contains many mysteries, and the full activity spectrum of checkpoint-blocking drugs, used alone or in combination, is currently the subject of intense study. Copyright © 2015 Elsevier Inc. All rights reserved.
          Article 0 comments Cited 1071 times – based on 0 reviews     Review now
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            Parallel reaction monitoring for high resolution and high mass accuracy quantitative, targeted proteomics.

            Amelia C Peterson, Jason D Russell, Derek J Bailey … (2012)
            Selected reaction monitoring on a triple quadrupole mass spectrometer is currently experiencing a renaissance within the proteomics community for its, as yet, unparalleled ability to characterize and quantify a set of proteins reproducibly, completely, and with high sensitivity. Given the immense benefit that high resolution and accurate mass instruments have brought to the discovery proteomics field, we wondered if highly accurate mass measurement capabilities could be leveraged to provide benefits in the targeted proteomics domain as well. Here, we propose a new targeted proteomics paradigm centered on the use of next generation, quadrupole-equipped high resolution and accurate mass instruments: parallel reaction monitoring (PRM). In PRM, the third quadrupole of a triple quadrupole is substituted with a high resolution and accurate mass mass analyzer to permit the parallel detection of all target product ions in one, concerted high resolution mass analysis. We detail the analytical performance of the PRM method, using a quadrupole-equipped bench-top Orbitrap MS, and draw a performance comparison to selected reaction monitoring in terms of run-to-run reproducibility, dynamic range, and measurement accuracy. In addition to requiring minimal upfront method development and facilitating automated data analysis, PRM yielded quantitative data over a wider dynamic range than selected reaction monitoring in the presence of a yeast background matrix because of PRM's high selectivity in the mass-to-charge domain. With achievable linearity over the quantifiable dynamic range found to be statistically equal between the two methods, our investigation suggests that PRM will be a promising new addition to the quantitative proteomics toolbox.
            Article 0 comments Cited 390 times – based on 0 reviews     Review now
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              Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study.

              Jedd Wolchok, Bart Neyns, Gerald P. Linette … (2010)
              Ipilimumab is a human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4 and has shown promising activity in advanced melanoma. We aimed to ascertain the antitumour efficacy of ipilimumab in patients with advanced melanoma. We undertook a randomised, double-blind, phase 2 trial in 66 centres from 12 countries. 217 patients with previously treated stage III (unresectable) or stage IV melanoma were randomly assigned a fixed dose of ipilimumab of either 10 mg/kg (n=73), 3 mg/kg (n=72), or 0.3 mg/kg (n=72) every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. Randomisation was done with a permuted block procedure, stratified on the basis of type of previous treatment. The primary endpoint was best overall response rate (the proportion of patients with a complete or partial response, according to modified WHO criteria). Efficacy analyses were done by intention to treat, whereas safety analyses included patients who received at least one dose of ipilimumab. This study is registered with ClinicalTrials.gov, number NCT00289640. The best overall response rate was 11.1% (95% CI 4.9-20.7) for 10 mg/kg, 4.2% (0.9-11.7) for 3 mg/kg, and 0% (0.0-4.9) for 0.3 mg/kg (p=0.0015; trend test). Immune-related adverse events of any grade arose in 50 of 71, 46 of 71, and 19 of 72 patients at doses of 10 mg/kg, 3 mg/kg, and 0.3 mg/kg, respectively; the most common grade 3-4 adverse events were gastrointestinal immune-related events (11 in the 10 mg/kg group, two in the 3 mg/kg group, none in the 0.3 mg/kg group) and diarrhoea (ten in the 10 mg/kg group, one in the 3 mg/kg group, none in the 0.3 mg/kg group). Ipilimumab elicited a dose-dependent effect on efficacy and safety measures in pretreated patients with advanced melanoma, lending support to further studies at a dose of 10 mg/kg. Bristol-Myers Squibb. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancer Biol Ther
                Journal ID (iso-abbrev): Cancer Biol. Ther
                Journal ID (publisher-id): KCBT
                Journal ID (publisher-id): kcbt20
                Title: Cancer Biology & Therapy
                Publisher: Taylor & Francis
                ISSN (Print): 1538-4047
                ISSN (Electronic): 1555-8576
                Publication date Collection: 2019
                Publication date (Electronic): 1 August 2019
                Publication date PMC-release: 1 August 2019
                Volume: 20
                Issue: 11
                Pages: 1366-1379
                Affiliations
                [a ]University of Arkansas for Medical Sciences, Department of Biochemistry and Molecular Biology , Little Rock, AR, USA
                [b ]University of Arkansas for Medical Sciences, Department of Pathology , Little Rock, AR, USA
                Author notes
                CONTACT Alan J. Tackett ajtackett@ 123456uams.edu Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205, USA;
                 Sara C. Shalin scshalin@ 123456uams.edu Department of Pathology and Dermatology, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205, USA.
                Article
                Publisher ID: 1640032
                DOI: 10.1080/15384047.2019.1640032
                PMC ID: 6804807
                PubMed ID: 31366280
                SO-VID: b02d05f0-5e50-49d5-9ee1-92c1ebafb83c
                Copyright © © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.

                History
                Date received : 8 February 2019
                Date revision received : 23 May 2019
                Date accepted : 23 June 2019
                Page count
                Figures: 2, References: 122, Pages: 14
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: P20GM121293
                This work was supported by the National Institutes of Health [P20GM121293].
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: melanoma,diagnosis,immunohistochemistry,treatment,immunotherapy,epigenetics
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: melanoma, diagnosis, immunohistochemistry, treatment, immunotherapy, epigenetics

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