Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children

Grill, Jacques; Sainte‐Rose, Christian; Jouvet, Anne; Gentet, Jean‐Claude; Lejars, Odile; Frappaz, Didier; Doz, François; Rialland, Xavier; Pichon, F.; Bertozzi, Anne‐Isabelle; Chastagner, Pascal; Couanet, D.; Habrand, Jean‐Louis; Raquin, Marie-Anne; Deley, Marie-Cécile Le; Kalifa, Chantal

doi:10.1016/s1470-2045(05)70252-7

Cited by 255 publications

(167 citation statements)

References 20 publications

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“…Even with multimodal strategies including surgery, radiation, and chemotherapy, tumor recurrence is frequent and most patients eventually succumb to progressive disease 4, 5, 6, 7, 8, 9. Conventional chemotherapy alone can effectively eliminate nonmetastatic MB, yet it is not sufficient to treat metastatic MB 10. Additionally, conventional chemotherapy allows to reduce the dose of radiation therapy; however, the inferior outcome of chemo‐radiation therapy is due to treatment interruption attributed to myelosuppression 11.…”

Section: Introductionmentioning

confidence: 99%

Targeting inhibitors of apoptosis proteins suppresses medulloblastoma cell proliferation via G2/M phase arrest and attenuated neddylation of p21

et al. 2018

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Medulloblastoma (MB) is the most common type of malignant childhood brain tumor. We previously showed that inhibitors of apoptosis proteins (IAP) small‐molecule inhibitors (LCL161 or LBW242) combined with chemotherapy have synergistic antiproliferative effects on MB cells. The synergistic antitumor effects of combination treatments happen through induction of autophagy and caspase‐3/7‐activated apoptosis. Here, we investigated the effects of IAP inhibitors or silencing IAP on cell cycle regulation. We discovered that treatment with IAP inhibitors or their combination with conventional chemotherapy (vincristine or cisplatin), as well as RNAi knockdown of cIAP1/2 or XIAP arrested MB cells in the G2/M phase through downregulation of cyclin B1‐CDK1 and cyclin A‐CDK1/2. Among these three IAPs, only silencing cIAP1 expression enhanced p21 dependent‐G2/M phase accumulation. IAP inhibitors reduced cIAP1 expression and increased p21 expression in time course experiments. Furthermore, cIAP1 can govern p21 proteasomal degradation via neddylation in lieu of ubiquitination. Inhibition of IAPs significantly abrogated cIAP1‐mediated p21 degradation. We also observed an inverse correlation between nuclear cIAP1 and nuclear p21 expressions in MB tumor tissues. These findings provide new mechanistic evidence of the influence of IAP inhibitors on MB cell proliferation through disruption of the cell cycle.

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Section: Introductionmentioning

confidence: 99%

Targeting inhibitors of apoptosis proteins suppresses medulloblastoma cell proliferation via G2/M phase arrest and attenuated neddylation of p21

et al. 2018

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“…[65][66][67] The results of the French Oncology Group (SFOP) study of children Ͻ 5 years old treated for 16 months with multiagent chemotherapy and deferring RT until relapse, emphasized the importance of radical surgery; the 5-year PFS of the 34 children with no metastatic disease (M0 stage) and GTR was 41% vs 0% for those with a subtotal resection. 68 Taken together, these studies suggest that infant medulloblastomas are responsive to chemotherapy, and that a gross total resection and M0 staging are significant prognostic factors. Such infants could reasonably be treated with relatively-prolonged chemotherapy, withholding RT until relapse; those with metastatic or residual tumor require a different approach.…”

Section: Common Pediatric Brain Tumors and Therapy Advancesmentioning

confidence: 87%

Advances in treatment of pediatric brain tumors

Robertson

2006

NeuroRX

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Summary:The long-term survival of children with brain tumor has improved considerably in the last three decades, owing to advances in neuroimaging, neurosurgical, and radiation therapy modalities, coupled with the application of conventional chemotherapy. MRI, MR spectroscopy and diffusion-weighted MRI have contributed to more accurate diagnosis, prognostication and better treatment planning. Neurosurgical treatment has been advanced by the use of functional MRI, and intraoperative image-guided stereotactic techniques and electrophysiologic monitoring. The use of 3-D conformal and intensitymodulated radiation therapy, stereotactic radiosurgery, and radiosensitizing agents has made radiation therapy safer and more effective. Conventional chemotherapy, administered either alone or combined with radiation therapy has improved survival and quality of life of children with brain tumors. These improved outcomes have also occurred, due, in part, to their treatment on collaborative national and international studies. Recent promising diagnostic and therapeutic strategies have resulted from advances in understanding molecular brain tumor biology. Important new approaches include the refinement of drug-delivery strategies, the evaluation of biologic markers to stratify patients for optimal treatment and to exploit these molecular differences using "targeted" therapeutic strategies. These approaches include blocking tumor cell drug resistance mechanisms, immunotherapy, inhibition of molecular signal transduction pathways important in tumorigenesis, anti-angiogenic therapy, and gene therapy. The thrust of such approaches for children with brain tumors is especially directed at reducing the toxicity of therapy and improving quality-of-life, as well as increasing disease-free survival.

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“…In pre-school age children with favourable presentations (non-metastatic, completely resected, desmoplastic histology) survival rates also exceed 70% in recently reported studies [54,109] using both low and high intensity chemotherapy schedules with or without intrathecal methotrexate and with or without involved field radiotherapy. The interaction between biological markers and these treatment strategies in this age group is yet to be studied [8,58,110].…”

Section: Drug Administrationmentioning

confidence: 91%

Medulloblastoma in childhood: revisiting intrathecal therapy in infants and children

Conroy

Garnett

Vloeberghs

et al. 2009

Cancer Chemother Pharmacol

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Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children

Cited by 255 publications

References 20 publications

Targeting inhibitors of apoptosis proteins suppresses medulloblastoma cell proliferation via G2/M phase arrest and attenuated neddylation of p21

Targeting inhibitors of apoptosis proteins suppresses medulloblastoma cell proliferation via G2/M phase arrest and attenuated neddylation of p21

Advances in treatment of pediatric brain tumors

Medulloblastoma in childhood: revisiting intrathecal therapy in infants and children

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