Current and Emerging Therapeutic Approaches for Extracranial Malignant Rhabdoid Tumors

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.

Automated summary

Extracranial malignant rhabdoid tumors (extracranial MRT) are rare and aggressive malignancies that mainly affect infants and children under 3 years old. They commonly occur in the kidneys and other soft tissues. The genetic origin of these tumors is linked to pathogenic variants in the SMARCB1 or SMARCA4 genes, which encode subunits of the SWI/SNF chromatin-remodeling complex. Although extracranial MRTs appear to be relatively homogeneous, recent epigenome analyses have revealed some degree of epigenetic heterogeneity. The use of intensified therapies has modestly improved survival rates, but high-risk patients still have a poor prognosis.