Journal Article

DKFZ-2026-02612

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Precision oncology in advanced melanoma: molecular landscapes and personalized therapy recommendations from the Molecular Tumor Board Freiburg.

Lowinus, T. ; Schipperges, V. ; Metzger, P. ; Brummer, T.DKFZ* ; Matysiak, U. ; Dopfer, E. P. ; Hess, M. E. ; Fahrner, M. ; Pauli, T. ; Blaumeiser, A. ; Becker, H.DKFZ* ; Kuehn, J. ; Rassner, M. ; Falkenstein, J. ; Bertemes, H. ; Bovio, P. ; Pinter, N. ; Cysar, S. ; Lehr, S. ; Wäsch, R. ; Gräßel, L.DKFZ* ; Eyerich, K. ; Schultheis, A. M.DKFZ* ; Schilling, O.DKFZ* ; Lassmann, S.DKFZ* ; Werner, M.DKFZ* ; Illert, A. L. ; Duyster, J.DKFZ* ; Zeiser, R.DKFZ* ; Miething, C. C. ; Börries, M.DKFZ* ; Meiss, F. ; Rafei, D.

2026
Springer Nature [London]

Abstract: Immune checkpoint inhibitors (ICIs) and BRAF/MEK kinase inhibitors have substantially improved survival in advanced melanoma; however, therapeutic resistance and severe toxicities underscore the ongoing need for alternative strategies. Here, we evaluate the clinical utility of multi-omic profiling, biomarker-stratified recommendations, and survival outcomes within a prospective cohort of 98 patients with advanced cutaneous or uveal melanoma evaluated by the Molecular Tumor Board Freiburg (MTB-FR) between 2021 and 2024. Completed profiling revealed at least one potential actionable target beyond classical BRAF V600 mutations in 83.8% of cases. Alterations in NRAS, atypical BRAF variants, CDK4/6 pathway amplifications, and DNA-damage response (DDR) gene mutations most frequently guided board recommendations. Biomarker-stratified therapies were recommended for 68.4% of patients, and personalized immunotherapy combinations for 72.4%. The treatment implementation rate was 33.8% (n = 27), achieving an overall disease control rate (DCR) of 42.9% and an overall response rate (ORR) of 10.7%. These findings demonstrate that comprehensive molecular profiling in a real-world setting uncovers actionable alterations, providing viable subsequent treatment avenues that may optimize outcomes for heavily pretreated melanoma patients beyond established standards of care. Ultimately, prospective, randomized, biomarker-driven trials remain essential to validate whether these individualized diagnostic strategies translate into a reproducible survival benefit.

Note: #DKTKZFB9#

---

Contributing Institute(s):

1. DKTK Koordinierungsstelle Freiburg (FR01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

---

Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---