RARE DISEASE
Rhabdoid tumor
Rhabdoid tumor
Rhabdoid tumor
Synonyms: Malignant rhabdoid tumor
Synonyms: Malignant rhabdoid tumor
Synonyms: Malignant rhabdoid tumor
Drug discovery
3
drugs
With orphan designations
Overview
Rhabdoid tumor is a rare, highly aggressive malignancy primarily affecting infants and young children, with peak incidence under age 4 [1][4][12]. These tumors most commonly arise in the CNS (atypical teratoid rhabdoid tumors, ATRT), kidneys (malignant rhabdoid tumors, MRT), or soft tissues [1][6][17]. Over 90% involve biallelic SMARCB1 inactivation, disrupting chromatin remodeling and driving epigenetic dysregulation [1][8][19]. Prognosis remains poor despite multimodal therapy, with survival rates heavily influenced by age and primary site [4][12][16].
Burden
Therapies
Multimodal approach: Maximal safe resection + intensive chemotherapy (vincristine, cyclophosphamide, cisplatin/etoposide) + age-adjusted radiotherapy [1][3][13]
High-dose chemotherapy with autologous stem cell rescue for consolidation [1][3][5]
Protocols: COG ACNS0333 (surgery → chemo → HDCT) vs. Eu-Rhab (anthracycline-based regimens + early RT) [1][3][5]
Categories: rare neoplastic diseases
Research Papers
1,006 drug discovery papers related to Rhabdoid tumor, with 8 first-in-class and 3 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
1,006 drug discovery papers related to Rhabdoid tumor, with 8 first-in-class and 3 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-01 | Molecular changes during AT/RT progression associated with epithelial-mesenchymal transition and extracellular matrix changes.
Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors during infancy and associated with a dismal prognosis. The majority of patients suffer from tumor progression or recurrence, but underlying mechanisms remain unknown. To better understand such mechanisms, we performed single-nucleus RNA sequencing (snRNAseq) of eight paired primary tumors and recurrences. Tumor cells and cells of the tumor microenvironment (TME) were analyzed separately. Potentially therapy-resistant tumor cells were identified through the comparison of global gene expression profiles between primary and recurrent tumor cell populations using CIBERSORT. Histopathology, in vitro experiments, bulk RNA sequencing, and survival analysis were performed for validation. Paired primary and recurrent AT/RT showed significant differences in their gene expression profiles. Potentially therapy-resistant AT/RT-MYC tumor cells revealed changes in the extracellular matrix (ECM) as well as altered developmental processes and immune signaling pathways. Respective gene signatures were correlated with inferior survival in AT/RT-MYC patients. Tumor cells of relapsed AT/RT-MYC underwent partial epithelial-mesenchymal transition (pEMT), a feature that was confirmed by immunohistochemistry (IHC) and by analyzing AT/RT cells after standard therapy in vitro. Together, we identified potential mechanisms of tumor relapse and therapy resistance in AT/RT, which could be employed to improve therapy in future.
2026-06-27 | A Three-Dimensional Culture-Drug Sensitivity Test Predicts MDM2 Inhibitor-Sensitivity in SMARCB1/INI1-Deficient Tumors.
Loss of SMARCB1/INI1 expression is a common feature of various types of tumors including malignant rhabdoid tumor, an aggressive cancer of children. Because SMARCB1/INI1 deficiency leads to genome-wide transcriptional dysregulation, identifying a specific therapeutic target that acts on a wide range of SMARCB1/INI1-deficient tumors has been challenging. This study aimed to establish if the personalized selection of effective drugs against SMARCB1/INI-deficient tumors is possible by in vitro drug sensitivity profiling. The in vitro drug sensitivity profiles of tumors from SMARCB1/INI1-deficient tumor cell line-derived mouse xenograft (CDX) models were evaluated by a short-term collagen gel-embedded three-dimensional culture-drug sensitivity test (3D-DST). With the 3D-DST, molecular targeting drugs, including inhibitors of aurora B kinase, mammalian target of rapamycin, mitogen-activated protein kinase, WNT/β-catenin, or mouse double minute 2 homolog (MDM2), were selected as therapeutic drug candidates in SMARCB1/INI1-deficient tumors. A CDX tumor, which was resistant to MDM2 inhibitors in the 3D-DST, expressed lower TP53 compared to an MDM2 inhibitor-sensitive tumor. In cultured cell lines, exposure to MI-773, a MDM2 inhibitor, disturbed the expression of a significant number of genes and induced p21 protein expression in MDM2 inhibitor-sensitive cells. However, such changes were not observed in resistant cells. These results suggest that 3D-DST can predict biologically relevant drug sensitivity profiles in SMARCB1/INI1-deficient tumors.
2026-06-26 | Development of a Genetically Engineered Porcine Model of Rhabdoid Tumor Predisposition Syndrome Type 1 (RTPS-1).
Background and Objectives: Among CNS malignancies arising in infancy, ATRT stands out as the most frequently diagnosed in children younger than six months. Disruption of the SMARCB1 gene underlies the overwhelming majority of cases. Progress toward effective treatment has been hampered by two persistent challenges. Current mouse models, while informative, fall short of reproducing the full clinical and biological picture of human ATRT, and their ability to predict therapeutic outcomes in patients remains uncertain. Compounding this, the rarity of the disease makes it difficult to assemble patient cohorts of sufficient size for meaningful clinical trials. At the molecular level, germline loss of SMARCB1 exons 4 and 5 has emerged as a particularly penetrant predisposing event, with affected individuals presenting at an earlier age than those harboring other mutation types. The porcine SMARCB1 gene offers a compelling basis for translational modeling as its protein product is identical to the human ortholog at every amino acid position across isoforms, a degree of conservation that exceeds what is seen in the mouse. Methods: Thus, we hypothesized that germline deletion of exons 4 and 5 would predispose heterozygote swine to ATRT development. In this manuscript, we describe the creation of an ATRT porcine model through a CRISPR/Cas9 mediated gene-editing approach. Results: 15 piglets were produced, two of which had confirmed SMARCB1 targeted excisions. However, none developed tumors. To induce further tumorigenicity, one pig with confirmed exons 4 and 5 excision was crossed with a pig with TP53 exon 2 truncation. In total, 11 piglets were born, of which one contained the original excision without a TP53 mutation. This piglet developed a spinal mass at the T1 level. Conclusion: To our knowledge, this is the first ATRT porcine model ever developed and provides proof-of-concept feasibility for large animal modeling of SMARCB1-deficient rhabdoid tumors. These findings support the continued development of porcine RTPS-1 models toward preclinical application.
2026-07-01 | Molecular changes during AT/RT progression associated with epithelial-mesenchymal transition and extracellular matrix changes.
Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors during infancy and associated with a dismal prognosis. The majority of patients suffer from tumor progression or recurrence, but underlying mechanisms remain unknown. To better understand such mechanisms, we performed single-nucleus RNA sequencing (snRNAseq) of eight paired primary tumors and recurrences. Tumor cells and cells of the tumor microenvironment (TME) were analyzed separately. Potentially therapy-resistant tumor cells were identified through the comparison of global gene expression profiles between primary and recurrent tumor cell populations using CIBERSORT. Histopathology, in vitro experiments, bulk RNA sequencing, and survival analysis were performed for validation. Paired primary and recurrent AT/RT showed significant differences in their gene expression profiles. Potentially therapy-resistant AT/RT-MYC tumor cells revealed changes in the extracellular matrix (ECM) as well as altered developmental processes and immune signaling pathways. Respective gene signatures were correlated with inferior survival in AT/RT-MYC patients. Tumor cells of relapsed AT/RT-MYC underwent partial epithelial-mesenchymal transition (pEMT), a feature that was confirmed by immunohistochemistry (IHC) and by analyzing AT/RT cells after standard therapy in vitro. Together, we identified potential mechanisms of tumor relapse and therapy resistance in AT/RT, which could be employed to improve therapy in future.
2026-06-27 | A Three-Dimensional Culture-Drug Sensitivity Test Predicts MDM2 Inhibitor-Sensitivity in SMARCB1/INI1-Deficient Tumors.
Loss of SMARCB1/INI1 expression is a common feature of various types of tumors including malignant rhabdoid tumor, an aggressive cancer of children. Because SMARCB1/INI1 deficiency leads to genome-wide transcriptional dysregulation, identifying a specific therapeutic target that acts on a wide range of SMARCB1/INI1-deficient tumors has been challenging. This study aimed to establish if the personalized selection of effective drugs against SMARCB1/INI-deficient tumors is possible by in vitro drug sensitivity profiling. The in vitro drug sensitivity profiles of tumors from SMARCB1/INI1-deficient tumor cell line-derived mouse xenograft (CDX) models were evaluated by a short-term collagen gel-embedded three-dimensional culture-drug sensitivity test (3D-DST). With the 3D-DST, molecular targeting drugs, including inhibitors of aurora B kinase, mammalian target of rapamycin, mitogen-activated protein kinase, WNT/β-catenin, or mouse double minute 2 homolog (MDM2), were selected as therapeutic drug candidates in SMARCB1/INI1-deficient tumors. A CDX tumor, which was resistant to MDM2 inhibitors in the 3D-DST, expressed lower TP53 compared to an MDM2 inhibitor-sensitive tumor. In cultured cell lines, exposure to MI-773, a MDM2 inhibitor, disturbed the expression of a significant number of genes and induced p21 protein expression in MDM2 inhibitor-sensitive cells. However, such changes were not observed in resistant cells. These results suggest that 3D-DST can predict biologically relevant drug sensitivity profiles in SMARCB1/INI1-deficient tumors.
2026-06-26 | Development of a Genetically Engineered Porcine Model of Rhabdoid Tumor Predisposition Syndrome Type 1 (RTPS-1).
Background and Objectives: Among CNS malignancies arising in infancy, ATRT stands out as the most frequently diagnosed in children younger than six months. Disruption of the SMARCB1 gene underlies the overwhelming majority of cases. Progress toward effective treatment has been hampered by two persistent challenges. Current mouse models, while informative, fall short of reproducing the full clinical and biological picture of human ATRT, and their ability to predict therapeutic outcomes in patients remains uncertain. Compounding this, the rarity of the disease makes it difficult to assemble patient cohorts of sufficient size for meaningful clinical trials. At the molecular level, germline loss of SMARCB1 exons 4 and 5 has emerged as a particularly penetrant predisposing event, with affected individuals presenting at an earlier age than those harboring other mutation types. The porcine SMARCB1 gene offers a compelling basis for translational modeling as its protein product is identical to the human ortholog at every amino acid position across isoforms, a degree of conservation that exceeds what is seen in the mouse. Methods: Thus, we hypothesized that germline deletion of exons 4 and 5 would predispose heterozygote swine to ATRT development. In this manuscript, we describe the creation of an ATRT porcine model through a CRISPR/Cas9 mediated gene-editing approach. Results: 15 piglets were produced, two of which had confirmed SMARCB1 targeted excisions. However, none developed tumors. To induce further tumorigenicity, one pig with confirmed exons 4 and 5 excision was crossed with a pig with TP53 exon 2 truncation. In total, 11 piglets were born, of which one contained the original excision without a TP53 mutation. This piglet developed a spinal mass at the T1 level. Conclusion: To our knowledge, this is the first ATRT porcine model ever developed and provides proof-of-concept feasibility for large animal modeling of SMARCB1-deficient rhabdoid tumors. These findings support the continued development of porcine RTPS-1 models toward preclinical application.
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Drug Discovery Landscape
3 orphan drug designations for Rhabdoid tumor.
3 orphan drug designations for Rhabdoid tumor.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
N-hydroxy-N-(methylacylfulvene)urea | small molecules | FDA | 2024-10-28 | — | Lantern Pharma Inc. |
O-18F-fluoroethyl-L-tyrosine | small molecules | FDA | 2019-05-08 | — | Advanced Imaging Projects, LLC |
tazemetostat | small molecules | FDA | 2016-02-04 | — | Epizyme Inc. |
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