Cancer Management and Research (Feb 2022)
Current and Emerging Therapeutic Approaches for Extracranial Malignant Rhabdoid Tumors
Abstract
Karolina Nemes,1 Pascal D Johann,1,2 Stefanie Tüchert,3 Patrick Melchior,4 Christian Vokuhl,5 Reiner Siebert,6 Rhoikos Furtwängler,7 Michael C Frühwald1 1Paediatrics and Adolescent Medicine, Swabian Children’s Cancer Center, University Medical Center Augsburg, Augsburg, Germany; 2Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; 3Department of Diagnostic and Interventional Radiology, University Hospital Augsburg, Augsburg, Germany; 4Department of Radiation Oncology, University of Saarland, Homburg, Germany; 5Section of Pediatric Pathology, Department of Pathology, University Hospital Bonn, Bonn, Germany; 6Institute of Human Genetics, Ulm University & Ulm University Medical Center, Ulm, Germany; 7Department of Pediatric Hematology and Oncology, University of Saarland, Homburg, GermanyCorrespondence: Michael C FrühwaldEU-RHAB Registry, Swabian Children’s Cancer Center, Paediatrics and Adolescent Medicine, University Medical Center Augsburg, Stenglinstr. 2, Augsburg, 86156, Germany, Tel +49 821 400 9342, Fax +49 821 400 179201, Email [email protected]: Extracranial malignant rhabdoid tumors (extracranial MRT) are rare, highly aggressive malignancies affecting mainly infants and children younger than 3 years. Common anatomic sites comprise the kidneys (RTK – rhabdoid tumor of kidney) and other soft tissues (eMRT – extracranial, extrarenal malignant rhabdoid tumor). The genetic origin of these diseases is linked to biallelic pathogenic variants in the genes SMARCB1, or rarely SMARCA4, encoding subunits of the SWI/SNF chromatin-remodeling complex. Even if extracranial MRT seem to be quite homogeneous, recent epigenome analyses reveal a certain degree of epigenetic heterogeneity. Use of intensified therapies has modestly improved survival for extracranial MRT. Patients at standard risk profit from conventional therapies; most high-risk patients still experience a dismal course and often therapy resistance. Discoveries of clinical and molecular hallmarks and the exploration of experimental therapeutic approaches open exciting perspectives for clinical and molecularly stratified experimental treatment approaches. To ultimately improve the outcome of patients with extracranial MRTs, they need to be characterized and stratified clinically and molecularly. High-risk patients need novel therapeutic approaches including selective experimental agents in phase I/II clinical trials.Keywords: extracranial malignant rhabdoid tumors, eMRT, RTK, experimental therapy, immunotherapy
