Clinical protein science in translational medicine targeting malignant melanoma

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Clinical protein science in translational medicine targeting malignant melanoma

Gil, Jeovanis (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Betancourt, Lazaro Hiram (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Pla, Indira (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital

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Sanchez, Aniel (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital

Appelqvist, Roger (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Miliotis, Tasso (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups,AstraZeneca, Sweden

Kuras, Magdalena (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Oskolas, Henriette (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Kim, Yonghyo (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Horvath, Zsolt (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Eriksson, Jonatan (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Berge, Ethan (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Burestedt, Elisabeth (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Jönsson, Göran (författare): Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,Lund Melanoma Study Group,Lund University Research Groups

Baldetorp, Bo (författare): Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine

Ingvar, Christian (författare): Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Lund Melanoma Study Group,Lund University Research Groups

Olsson, Håkan (författare): Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Melanoma Study Group,Lund University Research Groups

Lundgren, Lotta (författare): Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital

Horvatovich, Peter (författare): University of Groningen

Murillo, Jimmy Rodriguez (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Sugihara, Yutaka (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Welinder, Charlotte (författare): Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine

Wieslander, Elisabet (författare): Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine

Lee, Boram (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Lindberg, Henrik (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Pawłowski, Krzysztof (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups,Warsaw University of Life Sciences

Kwon, Ho Jeong (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups,Yonsei University

Doma, Viktoria (författare): Semmelweis University

Timar, Jozsef (författare): Semmelweis University

Karpati, Sarolta (författare): Semmelweis University

Szasz, A. Marcell (författare): Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Semmelweis University

Németh, István Balázs (författare): University of Szeged

Nishimura, Toshihide (författare): Tokyo Medical University,St. Marianna University School of Medicine

Corthals, Garry (författare): University of Amsterdam

Rezeli, Melinda (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups

Knudsen, Beatrice (författare): Cedars-Sinai Medical Center

Malm, Johan (författare): Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups

Marko-Varga, György (författare): Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups,Yonsei University,Tokyo Medical University

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(creator_code:org_t)

2019-03-21
2019
Engelska.
Ingår i: Cell Biology and Toxicology. - : Springer Science and Business Media LLC. - 0742-2091 .- 1573-6822. ; 35:4, s. 293-332

Relaterad länk:: http://dx.doi.org/10... (free); visa fler...; https://link.springe...; https://lup.lub.lu.s...; https://doi.org/10.1...; visa färre...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

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Melanoma of the skin is the sixth most common type of cancer in Europe and accounts for 3.4% of all diagnosed cancers. More alarming is the degree of recurrence that occurs with approximately 20% of patients lethally relapsing following treatment. Malignant melanoma is a highly aggressive skin cancer and metastases rapidly extend to the regional lymph nodes (stage 3) and to distal organs (stage 4). Targeted oncotherapy is one of the standard treatment for progressive stage 4 melanoma, and BRAF inhibitors (e.g. vemurafenib, dabrafenib) combined with MEK inhibitor (e.g. trametinib) can effectively counter BRAFV600E-mutated melanomas. Compared to conventional chemotherapy, targeted BRAFV600E inhibition achieves a significantly higher response rate. After a period of cancer control, however, most responsive patients develop resistance to the therapy and lethal progression. The many underlying factors potentially causing resistance to BRAF inhibitors have been extensively studied. Nevertheless, the remaining unsolved clinical questions necessitate alternative research approaches to address the molecular mechanisms underlying metastatic and treatment-resistant melanoma. In broader terms, proteomics can address clinical questions far beyond the reach of genomics, by measuring, i.e. the relative abundance of protein products, post-translational modifications (PTMs), protein localisation, turnover, protein interactions and protein function. More specifically, proteomic analysis of body fluids and tissues in a given medical and clinical setting can aid in the identification of cancer biomarkers and novel therapeutic targets. Achieving this goal requires the development of a robust and reproducible clinical proteomic platform that encompasses automated biobanking of patient samples, tissue sectioning and histological examination, efficient protein extraction, enzymatic digestion, mass spectrometry–based quantitative protein analysis by label-free or labelling technologies and/or enrichment of peptides with specific PTMs. By combining data from, e.g. phosphoproteomics and acetylomics, the protein expression profiles of different melanoma stages can provide a solid framework for understanding the biology and progression of the disease. When complemented by proteogenomics, customised protein sequence databases generated from patient-specific genomic and transcriptomic data aid in interpreting clinical proteomic biomarker data to provide a deeper and more comprehensive molecular characterisation of cellular functions underlying disease progression. In parallel to a streamlined, patient-centric, clinical proteomic pipeline, mass spectrometry–based imaging can aid in interrogating the spatial distribution of drugs and drug metabolites within tissues at single-cell resolution. These developments are an important advancement in studying drug action and efficacy in vivo and will aid in the development of more effective and safer strategies for the treatment of melanoma. A collaborative effort of gargantuan proportions between academia and healthcare professionals has led to the initiation, establishment and development of a cutting-edge cancer research centre with a specialisation in melanoma and lung cancer. The primary research focus of the European Cancer Moonshot Lund Center is to understand the impact that drugs have on cancer at an individualised and personalised level. Simultaneously, the centre increases awareness of the relentless battle against cancer and attracts global interest in the exceptional research performed at the centre.

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Clinical protein science in translational medicine targeting malignant melanoma

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