RARE DISEASE
Central nervous system embryonal tumor
Central nervous system embryonal tumor
Central nervous system embryonal tumor
Synonyms: CNS PNET, Central nervous system primitive neuroectodermal tumor
Synonyms: CNS PNET, Central nervous system primitive neuroectodermal tumor
Synonyms: CNS PNET, Central nervous system primitive neuroectodermal tumor
Drug discovery
1
drug
With orphan designation
Overview
Central nervous system (CNS) embryonal tumors are aggressive pediatric malignancies originating from neuroectodermal cells, classified by molecular profiles per WHO guidelines [1][6][13]. Key entities include medulloblastoma, atypical teratoid/rhabdoid tumor (ATRT), and embryonal tumor with multilayered rosettes (ETMR). Tumors without definitive molecular signatures are designated NOS/NEC [1][16]. Prognosis varies by molecular subtype, with 5-year survival ranging from 10%-47% for advanced cases [3][13][17]. Multimodal treatment is standard, but molecular heterogeneity complicates therapeutic precision [8][13].
Therapies
Maximal safe resection + craniospinal radiation (age-dependent) + platinum-based chemotherapy [8][17][20]
Molecularly guided therapies (e.g., TOP1 inhibitors for ETMR, targeted agents for NEC tumors with actionable mutations) [3][8][13]
Ongoing trials explore epigenetic modulators and differentiation therapies [3][8][13]
Categories: rare neoplastic diseases, rare neurological diseases
Research Papers
221 drug discovery papers about Central nervous system embryonal tumor, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
221 drug discovery papers about Central nervous system embryonal tumor, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-30 | High-dose chemotherapy with autologous stem cell rescue in children under 5 years of age with central nervous system embryonal tumors: results from a prospective cohort in an upper-middle-income country
PURPOSE: High-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) has been employed to mitigate the long-term side effects of radiotherapy and improve survival outcomes in infants with embryonal central nervous system (CNS) tumors. METHODS: This prospective study, supported by federal funding from the National Oncological Care Support Program, included children younger than 5 years of age with newly diagnosed CNS embryonal tumors treated with surgery and HDCT/ASCR. RESULTS: Between 2016 and 2019, 36 patients were included: 22 with medulloblastoma (MB) and 14 with other CNS embryonal tumors. In the MB cohort, the mean age was 2.5 years, 13 were male. Gross total resection (GTR) was achieved in 18 patients; 15 had non-metastatic disease (M0). Among non-MB patients, the mean age was 2.7 years, 11 were female. Nine patients had GTR; 12 had M0. According to the MB molecular subgroup, the 2- and 5-year event-free survival (EFS) rates for the SHH subgroup were 76.9%, and overall survival (OS) was 92.3%. For the non-WNT/non-SHH subgroup, the 2- and 5-year EFS rates were 33.3% and 22.2%, and OS, 66.7% and 55.6%, respectively. Two SHH and five non-WNT/non-SHH patients were successfully salvaged with craniospinal irradiation after a mean of 12 months (range, 7-36 months). Among non-MB patients, the 2- and 5-year EFS and OS were 28.6/19.0% and 42.9/32.1%, respectively. All patients developed grade 3-4 mucositis/typhlitis and febrile neutropenia and 13.9% invasive fungal infections during HDCT. CONCLUSION: HDCT/ASCR is feasible in a middle-income country setting and provides favorable outcomes in SHH medulloblastoma. However, prognosis remains poor for non-SHH MB and other embryonal tumors, highlighting the need for novel molecularly guided therapies.
2026-06-23 | ID #993 Intravenous GD2 CAR T-Cell Therapy in Pediatric and Young Adult Central Nervous System Tumors: Preliminary Data
Abstract Background Immunotherapy with chimeric antigen receptor (CAR) T cells targeting the disialoganglioside GD2 may represent a therapeutic option for pediatric patients with high-grade central nervous system (CNS) tumors. Here, we report preliminary findings from an ongoing academic phase I clinical trial (NCT05298995) conducted at the Bambino Gesù Children Hospital in Rome, Italy. Methods This phase-I multi-arm, dose-escalation/descalation trial enrolled patients aged 6 months-30 years with relapsed/refractory CNS tumors to evaluate the safety/feasibility of third-generation GD2 CAR-T cells expressing an inducible caspase-9 suicide gene (GD2-CART01) intravenously administered. Five dose levels and three treatment arms were planned: Arm A (embryonal tumors), Arm B (hemispheric high-grade gliomas), and Arm C (diffuse midline gliomas and rare CNS tumors). Results Twenty-two patients have been enrolled so far; five were screening failures and 17 received GD2-CART01. Cytokine release syndrome occurred in 97% of patients. Immune effector cell–associated neurotoxicity syndrome (ICANS) was observed in 29% of patients, exclusively in Arm A, while tumor inflammation–associated neurotoxicity (TIAN) occurred in 23% and was restricted to Arms B and C. Hematologic toxicity was observed in all patients. Steroids were required in 37% of patients and AP1903 in 21%. Two dose-limiting toxicities were reported. CAR T-cell expansion was detected in all patients in blood and cerebrospinal fluid, with persistence up to 18 months post-infusion in one patient with medulloblastoma. At week 6, the disease control rate was 42% (18% partial response, 24% stable disease). Median overall survival (OS) was 6.6 months (range, 1.2–24.5), with six-month and one-year OS rates of 47% and 32.3%, respectively. The most favorable outcomes were observed in one patient with diffuse intrinsic pontine glioma alive at one year post-infusion and in three patients with medulloblastoma treated at low disease burden. Conclusions GD2-CART01 is feasible in pediatric and young adult patients with high-risk CNS tumors, with encouraging preliminary efficacy.
2026-06-23 | ID #662 Treatment approaches for CNS tumors with BCOR ITD
Abstract High grade neuroepithelial tumors of the central nervous system (CNS) with BCL-6 corepressor (BCOR) with internal tandem duplication (ITD) are rare and aggressive pediatric tumors without standardized treatment options. These tumors are histologically embryonal tumors and molecular profiling is necessary to establish the diagnosis. These patients are treated per available case reports and case series. We are presenting our institutional experience with two cases. Case1 2-year-old presented with right hand weakness. Imaging showed mass measuring 10.6cm arising from left cerebral hemisphere, negative spine imaging. She underwent gross total resection (GTR). Pathology showed high-grade neuroepithelial tumor with BCOR ITD. Treated per Children’s Oncology Group protocol ACNS0334 with three intensive induction cycles and three autologous transplants. Two years later she presented with right-sided hemiplegia and partial seizure. Imaging showed a 2.1cm nodule in the surgical bed with hemorrhage. Underwent GTR, craniospinal irradiation to 26.3Gy, tumor boost to 56.5Gy and chemotherapy with bevacizumab, irinotecan and temozolomide, and now in remission over 6 years from recurrence. Case 2 2-year-old presented with headache and abnormal gait and found to have a right frontal lobe mixed solid and cystic mass, negative spine imaging. Bifrontal craniotomy was performed to achieve GTR. The pathology showed malignant CNS tumor with BCOR ITD. The patient was treated similarly to case 1 with three intensive induction chemotherapy cycles followed by high-dose chemotherapy with autologous transplant, and then focal radiation to the primary tumor site to 51Gy. The patient is in remission for the past 6 months. Conclusion Even though diagnostic challenges are being met through molecular profiling, the treatment options remain unstandardized. Both patients did well with a combination of intensive chemotherapy, autologous stem cell transplant and irradiation and remain disease-free. This case series emphasizes the need to standardize treatment approaches for CNS tumors with BCOR ITD.
2026-06-30 | High-dose chemotherapy with autologous stem cell rescue in children under 5 years of age with central nervous system embryonal tumors: results from a prospective cohort in an upper-middle-income country
PURPOSE: High-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) has been employed to mitigate the long-term side effects of radiotherapy and improve survival outcomes in infants with embryonal central nervous system (CNS) tumors. METHODS: This prospective study, supported by federal funding from the National Oncological Care Support Program, included children younger than 5 years of age with newly diagnosed CNS embryonal tumors treated with surgery and HDCT/ASCR. RESULTS: Between 2016 and 2019, 36 patients were included: 22 with medulloblastoma (MB) and 14 with other CNS embryonal tumors. In the MB cohort, the mean age was 2.5 years, 13 were male. Gross total resection (GTR) was achieved in 18 patients; 15 had non-metastatic disease (M0). Among non-MB patients, the mean age was 2.7 years, 11 were female. Nine patients had GTR; 12 had M0. According to the MB molecular subgroup, the 2- and 5-year event-free survival (EFS) rates for the SHH subgroup were 76.9%, and overall survival (OS) was 92.3%. For the non-WNT/non-SHH subgroup, the 2- and 5-year EFS rates were 33.3% and 22.2%, and OS, 66.7% and 55.6%, respectively. Two SHH and five non-WNT/non-SHH patients were successfully salvaged with craniospinal irradiation after a mean of 12 months (range, 7-36 months). Among non-MB patients, the 2- and 5-year EFS and OS were 28.6/19.0% and 42.9/32.1%, respectively. All patients developed grade 3-4 mucositis/typhlitis and febrile neutropenia and 13.9% invasive fungal infections during HDCT. CONCLUSION: HDCT/ASCR is feasible in a middle-income country setting and provides favorable outcomes in SHH medulloblastoma. However, prognosis remains poor for non-SHH MB and other embryonal tumors, highlighting the need for novel molecularly guided therapies.
2026-06-23 | ID #993 Intravenous GD2 CAR T-Cell Therapy in Pediatric and Young Adult Central Nervous System Tumors: Preliminary Data
Abstract Background Immunotherapy with chimeric antigen receptor (CAR) T cells targeting the disialoganglioside GD2 may represent a therapeutic option for pediatric patients with high-grade central nervous system (CNS) tumors. Here, we report preliminary findings from an ongoing academic phase I clinical trial (NCT05298995) conducted at the Bambino Gesù Children Hospital in Rome, Italy. Methods This phase-I multi-arm, dose-escalation/descalation trial enrolled patients aged 6 months-30 years with relapsed/refractory CNS tumors to evaluate the safety/feasibility of third-generation GD2 CAR-T cells expressing an inducible caspase-9 suicide gene (GD2-CART01) intravenously administered. Five dose levels and three treatment arms were planned: Arm A (embryonal tumors), Arm B (hemispheric high-grade gliomas), and Arm C (diffuse midline gliomas and rare CNS tumors). Results Twenty-two patients have been enrolled so far; five were screening failures and 17 received GD2-CART01. Cytokine release syndrome occurred in 97% of patients. Immune effector cell–associated neurotoxicity syndrome (ICANS) was observed in 29% of patients, exclusively in Arm A, while tumor inflammation–associated neurotoxicity (TIAN) occurred in 23% and was restricted to Arms B and C. Hematologic toxicity was observed in all patients. Steroids were required in 37% of patients and AP1903 in 21%. Two dose-limiting toxicities were reported. CAR T-cell expansion was detected in all patients in blood and cerebrospinal fluid, with persistence up to 18 months post-infusion in one patient with medulloblastoma. At week 6, the disease control rate was 42% (18% partial response, 24% stable disease). Median overall survival (OS) was 6.6 months (range, 1.2–24.5), with six-month and one-year OS rates of 47% and 32.3%, respectively. The most favorable outcomes were observed in one patient with diffuse intrinsic pontine glioma alive at one year post-infusion and in three patients with medulloblastoma treated at low disease burden. Conclusions GD2-CART01 is feasible in pediatric and young adult patients with high-risk CNS tumors, with encouraging preliminary efficacy.
2026-06-23 | ID #662 Treatment approaches for CNS tumors with BCOR ITD
Abstract High grade neuroepithelial tumors of the central nervous system (CNS) with BCL-6 corepressor (BCOR) with internal tandem duplication (ITD) are rare and aggressive pediatric tumors without standardized treatment options. These tumors are histologically embryonal tumors and molecular profiling is necessary to establish the diagnosis. These patients are treated per available case reports and case series. We are presenting our institutional experience with two cases. Case1 2-year-old presented with right hand weakness. Imaging showed mass measuring 10.6cm arising from left cerebral hemisphere, negative spine imaging. She underwent gross total resection (GTR). Pathology showed high-grade neuroepithelial tumor with BCOR ITD. Treated per Children’s Oncology Group protocol ACNS0334 with three intensive induction cycles and three autologous transplants. Two years later she presented with right-sided hemiplegia and partial seizure. Imaging showed a 2.1cm nodule in the surgical bed with hemorrhage. Underwent GTR, craniospinal irradiation to 26.3Gy, tumor boost to 56.5Gy and chemotherapy with bevacizumab, irinotecan and temozolomide, and now in remission over 6 years from recurrence. Case 2 2-year-old presented with headache and abnormal gait and found to have a right frontal lobe mixed solid and cystic mass, negative spine imaging. Bifrontal craniotomy was performed to achieve GTR. The pathology showed malignant CNS tumor with BCOR ITD. The patient was treated similarly to case 1 with three intensive induction chemotherapy cycles followed by high-dose chemotherapy with autologous transplant, and then focal radiation to the primary tumor site to 51Gy. The patient is in remission for the past 6 months. Conclusion Even though diagnostic challenges are being met through molecular profiling, the treatment options remain unstandardized. Both patients did well with a combination of intensive chemotherapy, autologous stem cell transplant and irradiation and remain disease-free. This case series emphasizes the need to standardize treatment approaches for CNS tumors with BCOR ITD.
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Drug Discovery Landscape
1 orphan drug designation for Central nervous system embryonal tumor.
1 orphan drug designation for Central nervous system embryonal tumor.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
genetically engineered herpes simplex virus | gene therapies | FDA | 2019-05-09 | — | Aettis, Inc. |
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