This is an exploratory prospective translational multicentre study. Melanoma is the 5th most common cancer diagnosed in Ireland and its incidence among women and men is above the European average.

Following treatment the elimination of cancer cells ultimately occurs by the activation of apoptotic cell death pathways. The SYS-ACT approach builds on a combination of mathematical systems of modelling, quantitative biochemistry and cell biology, and specifically predicts the drug responsiveness of melanoma cell lines to various apoptosis-inducing treatments.

The investigators propose to validate the SYS-ACT approach and application in a translational systems medicine study.

Inclusion Criteria:

1. Patients ≥ 18 years of age.

2. Patient must be able to give own signed informed consent.

3. Patients that present with advanced or metastatic (stage III/IV) malignant melanoma of the skin.

4. Patients that are planned to receive either:

   • Adjuvant treatment
   • 1st line treatment for metastatic disease
   • 2nd line treatment for metastatic disease

5. Patients with prior adjuvant treatment are allowed.

6. Patients receiving planned standard treatment of one or more of the following:

   • Chemotherapy regimens containing DTIC, TMZ and/or cisplatin
   • Immunotherapy (for example ipilimumab and/or anti-PD-L1/PD-1 therapies)
   • BRAF and/or MEK inhibitors

7. Patients were FFPE and fresh frozen tissue is available (both mandatory).

Exclusion Criteria:

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Patients must have a diagnosis of advanced or metastatic melanoma of the skin