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.