Molecular targeted therapies for pediatric atypical teratoid/rhabdoid tumors

Abstract

Atypical teratoid/rhabdoid tumors (AT/RTs) are lethal central nervous system tumors, which are primarily diagnosed in infants. Current treatments for AT/RTs include surgery, radiotherapy, and chemotherapy; these treatments have poor prognoses and challenging side effects. The pivotal genetic event in AT/RT pathogenesis comprises the inactivation of SMARCB1 or SMARCA4. Recent epigenetic studies have demonstrated mutual and subtype-specific epigenetic derangements that drive tumorigenesis; the exploitation of these potential targets might improve the dismal treatment outcomes of AT/RTs. This review aims to summarize the literature concerning targeted molecular therapies for pediatric AT/RTs.

An adult with recurrent atypical teratoid rhabdoid tumor of the spine

“…There is an increased emphasis on studies to assess the effectiveness of molecularly targeted therapies for AT/RTs. AT/RTs are thought to result from chromatin remodeling due to the inactivation of SMARCB1 or SMARCA4 , histone modification due to reduced regulation of H3K27, and DNA methylation due to dysregulation of Notch/sonic hedgehog (ATRT-SHH), tyrosinase enzyme (ATRT-TYR), and the MYC oncogene (ATRT-MYC) [ 21 , 23 ]. Inhibitors used in targeted therapy clinical trials to treat AT/RT include mTOR (drug: Sirolimus), EZH2 (drug: Tazemetostat), and CDK4/6 (drug: Ribociclib) [ 24–26 ].…”

Spinal Atypical Teratoid/Rhabdoid Tumor in an Adult: Case Report and Comprehensive Review of the Literature

“…Several chemotherapeutic regimens have been described for the treatment of ATRT, including the modified Intergroup Rhabdomyosarcoma III protocol, St. Jude medulloblastoma protocol, malignant rhabdoid tumor protocol and more [11,13,[35][36][37][38]. The majority of chemotherapy agents in these protocols include vincristine, cyclophosphamide, cisplatin, and etoposide.…”

SMARCB1-Deficient Cancers: Novel Molecular Insights and Therapeutic Vulnerabilities

“…Recent studies have suggested that these subgroup-specific epigenetic and transcriptomic profiles may be utilized to identify therapeutic vulnerabilities and provide targeted treatment that may improve current clinical outcomes [ 141 ]. Some of these novel molecular therapies for ATRT are discussed in the following section.…”