Molekulare Onkologie – wo stehen wir heute?

Tumoren entstehen durch molekulare Veränderungen von Zellen. Neue Technologien und Medikamente erlauben eine schnellere und zuverlässige Diagnostik sowie zielgerichtete Behandlung von immer mehr molekularen Alterationen. In diesem Beitrag werden aktuelle Standards und Herausforderungen einer personalisierten Krebstherapie diskutiert.

Schlüsselwörter

Präzisionsonkologie - Molekulares Tumorboard - Targeted Therapy - Personalisierte Therapie

• Literatur

• 1 Cremolini C, Loupakis F, Antoniotti C. et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol 2015; 16: 1306-1315
• 2 Pezo RC, Bedard PL. Definition: Translational and Personalised Medicine, Biomarkers, Pharmacodynamics. In: ESMO Handbook of Translational Research. 2015
• 3 Kopetz S, Guthrie KA, Morris VK. et al. Randomized Trial of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF-Mutant Metastatic Colorectal Cancer (SWOG S1406). J Clin Oncol 2021; 39: 285-294
• 4 Hobbs BP, Pestana RC, Zabor EC. et al. Basket Trials: Review of Current Practice and Innovations for Future Trials. J Clin Oncol 2022; 40
• 5 Hyman DM, Puzanov I, Subbiah V. et al. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med 2015; 373: 726-736
• 6 Salama AKS, Li S, Macrae ER. et al. Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Results of the NCI-MATCH Trial Subprotocol H. J Clin Oncol 2020; 38: 3895-3904
• 7 Sbaraglia M, Bellan E, Dei Tos AP. The 2020 WHO Classification of Soft Tissue Tumours: news and perspectives. Pathologica 2021; 113: 70-84
• 8 Drilon A, Laetsch TW, Kummar S. et al. Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children. New England Journal of Medicine 2018; 378: 731-739
• 9 André T, Shiu K-K, Kim TW. et al. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med 2020; 383: 2207-2218
• 10 Steuten L, Goulart B, Meropol NJ. et al. Cost Effectiveness of Multigene Panel Sequencing for Patients With Advanced Non-Small-Cell Lung Cancer. JCO Clin Cancer Inform 2019; 3: 1-10
• 11 Horak P, Heining C, Kreutzfeldt S. et al. Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers. Cancer Discov 2021; candisc. 0126 2021;
• 12 Massard C, Michiels S, Ferté C. et al. High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial. Cancer Discov 2017;
• 13 Capper D, Jones DTW, Sill M. et al. DNA methylation-based classification of central nervous system tumours. Nature 2018; 555: 469-474
• 14 Cervantes A, Adam R, Roselló S. et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2023; 34
• 15 Hendriks LE, Kerr K, Menis J. et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up†. Annals of Oncology 2023; 0
• 16 le Tourneau C, Delord JP, Gonçalves A. et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol 2015; 16: 1324-1334
• 17 Rieke DT, de Bortoli T, Horak P. et al. Feasibility and outcome of reproducible clinical interpretation of high-dimensional molecular data: a comparison of two molecular tumor boards. BMC Med 2022; 20
• 18 Rodon J, Soria JC, Berger R. et al. Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial. Nat Med 2019; 25: 751-758
• 19 Sicklick JK, Kato S, Okamura R. et al. Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nat Med 2019; 25: 744-750
• 20 Friedman C, Swanton C, Spigel D. et al. 66O MyPathway: A multiple target, multiple basket study of targeted treatments in tissue-agnostic cohorts of patients (pts) with advanced solid tumors. Annals of Oncology 2022; 33: S571
• 21 Kurzrock R, Bowles DW, Kang H. et al. Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: results from MyPathway, a phase IIa multiple basket study. Ann Oncol 2020; 31: 412-421
• 22 Lamping M, Benary M, Leyvraz S. et al. Support of a molecular tumour board by an evidence-based decision management system for precision oncology. Eur J Cancer 2020; 127: 41-51