sirolimus and Ependymoma

sirolimus has been researched along with Ependymoma* in 3 studies

Other Studies

3 other study(ies) available for sirolimus and Ependymoma

ArticleYear
Systemic chemotherapy of pediatric recurrent ependymomas: results from the German HIT-REZ studies.
    Journal of neuro-oncology, 2021, Volume: 155, Issue:2

    Survival in recurrent ependymoma (EPN) depends mainly on the extent of resection achieved. When complete resection is not feasible, chemotherapy is often used to extend progression-free and overall survival. However, no consistent effect of chemotherapy on survival has been found in patients with recurrent EPN.. Systemic chemotherapeutic treatment of 138 patients enrolled in the German HIT-REZ-studies was analyzed. Survival depending on the use of chemotherapy, disease-stabilization rates (RR), duration of response (DOR) and time to progression (TTP) were estimated.. Median age at first recurrence was 7.6 years (IQR: 4.0-13.6). At first recurrence, median PFS and OS were 15.3 (CI 13.3-20.0) and 36.9 months (CI 29.7-53.4), respectively. The Hazard Ratio for the use of chemotherapy in local recurrences in a time-dependent Cox-regression analysis was 0.99 (CI 0.74-1.33). Evaluable responses for 140 applied chemotherapies were analyzed, of which sirolimus showed the best RR (50%) and longest median TTP [11.51 (CI 3.98; 14.0) months] in nine patients, with the strongest impact found when sirolimus was used as a monotherapy. Seven patients with progression-free survival > 12 months after subtotal/no-resection facilitated by chemotherapy were found. No definitive survival advantage for any drug in a specific molecularly defined EPN type was found.. No survival advantage for the general use of chemotherapy in recurrent EPN was found. In cases with incomplete resection, chemotherapy was able to extend survival in individual cases. Sirolimus showed the best RR, DOR and TTP out of all drugs analyzed and may warrant further investigation.

    Topics: Adolescent; Brain Neoplasms; Child; Child, Preschool; Ependymoma; Germany; Humans; Neoplasm Recurrence, Local; Sirolimus; Treatment Outcome

2021
Inhibition of the NOTCH pathway using γ-secretase inhibitor RO4929097 has limited antitumor activity in established glial tumors.
    Anti-cancer drugs, 2015, Volume: 26, Issue:3

    Notch signaling is altered in many cancers. Our previous findings in primary pediatric ependymoma support a role for NOTCH in glial oncogenesis. The present study evaluates the γ-secretase inhibitor RO4929097 in glial tumor models. The expression of Notch pathway genes was evaluated using real-time RT-PCR in 21 ependymoma and glioma models. NOTCH1 mutations were analyzed by DNA sequencing. RO4929097 activity was evaluated in vitro and in vivo, as a single agent and in combination, in glioma and ependymoma models. Notch pathway genes are overexpressed in ependymomas and gliomas along with FBXW7 downregulation. NOTCH1 mutations in the TAD domain were observed in 20% (2/10) of ependymoma primary cultures. Blocking the Notch pathway with the γ-secretase inhibitor RO4929097 reduced cell density and viability in ependymoma short-term cultures. When combined with chemotherapeutic agents, RO4929097 enhanced temozolomide effects in ependymoma short-term cultures and potentiated the cytotoxicity of etoposide, cisplatinum, and temozolomide in glioma cells. RO4929097, in combined treatment with mTOR inhibition, potentiated cytotoxicity in vitro, but did not enhance antitumor effects in vivo. In contrast, RO4929097 enhanced irradiation effects in glioma and ependymoma xenografts and showed tumor growth inhibition in advanced-stage IGRG121 glioblastoma xenografts. RO4929097-mediated effects were independent of NOTCH1 mutation status or expression levels, but associated with low IL-6 levels. In established glial tumor models, NOTCH inhibition had limited effects as a single agent, but enhanced efficacy when combined with DNA-interfering agents. These preclinical data need to be considered for further clinical development of NOTCH inhibitors in glial tumors.

    Topics: Amyloid Precursor Protein Secretases; Animals; Antineoplastic Combined Chemotherapy Protocols; Benzazepines; Cell Line, Tumor; Cell Survival; Ependymoma; Gene Expression Regulation, Neoplastic; Glioma; Humans; Interleukin-6; Mice, Nude; Molecular Targeted Therapy; Protein Kinase Inhibitors; Receptor, Notch1; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases; Xenograft Model Antitumor Assays

2015
mTORC1 activation in childhood ependymoma and response to sirolimus.
    Journal of neuro-oncology, 2011, Volume: 103, Issue:3

    Recurrent ependymomas are considered rarely responsive to chemotherapy and often have a dismal prognosis after tumor progression. Below is a brief report of a 6 year old child with a multiply progressive ependymoma whose tumor had a near complete response to sirolimus that was durable for 18 months. Immunohistochemistry for phosphorylated S6, which has been reported to be associated with tumor sensitivity to mTORC1 inhibitors, was positive in this patient's tumor.

    Topics: Brain Neoplasms; Child, Preschool; Ependymoma; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Ribosomal Protein S6; Serine; Sirolimus; TOR Serine-Threonine Kinases

2011