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Emerging therapeutic targets for the treatment of malignant rhabdoid tumors.
Expert Opinion on Therapeutic Targets 2018 April
INTRODUCTION: Malignant Rhabdoid Tumor (MRT) is a rare and highly aggressive malignancy primarily affecting infants and young children. The most common anatomic locations are the central nervous system (AT/RT), the kidneys (RTK) and other soft tissues (eMRT). The genetic origin of this disease is linked to mutations in SMARCB1, a gene encoding a core subunit of the SWI/SNF chromatin-remodeling complex. Areas covered: Conventional multimodal treatment may offer a significant survival benefit to certain patients. It remains to be determined, however, which patients will prove resistant to chemotherapy and need novel therapeutic approaches. Herein we discuss key signal transduction pathways involved in the pathogenesis of rhabdoid tumors for potential targeted therapy (EZH2, DNMT, HDAC, CDK4/6/Cyclin D1/Rb, AURKA, SHH/GLI1, Wnt/ß-Catenin, immunotherapy). Additional agents currently evaluated in preclinical settings and experimental clinical trials are discussed. Expert opinion: MRTs are genetically homogeneous, but epigenetically distinct malignancies. While there is an abundance of experimental in vitro studies evaluating potential therapeutic avenues, a dearth of clinical trials specifically for this entity persists. In order to improve outcome patients need to be carefully stratified and treated by targeted therapies combined with conventional chemotherapy or with new, less selective experimental agents in phase I/II clinical trials.
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