Paediatric Strategy Forum for medicinal product development in mitogen-activated protein kinase pathway inhibitors: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration
As the mitogen-activated protein kinase (MAPK) signalling pathway is activated in many paediatric cancers, it is an important therapeutic target. Currently, a range of targeted MAPK pathway inhibitors are being developed in adults. However, MAPK signals through many cascades and feedback loops and p...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
14 October 2022
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| In: |
European journal of cancer
Year: 2022, Volume: 177, Pages: 120-142 |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2022.09.036 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.ejca.2022.09.036 Verlag, Volltext: https://www.sciencedirect.com/science/article/pii/S0959804922007766 
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| Author Notes: | Andrew DJ. Pearson, Carl Allen, Jason Fangusaro, Caroline Hutter, Olaf Witt, Susan Weiner, Gregory Reaman, Mark Russo, Pratiti Bandopadhayay, Sama Ahsan, Amy Barone, Elly Barry, Teresa de Rojas, Michael Fisher, Elizabeth Fox, Julia Glade Bender, Lia Gore, Darren Hargrave, Doug Hawkins, Brent Kreider, Abraham J. Langseth, Giovanni Lesa, Franca Ligas, Marcelo Marotti, Lynley V. Marshall, Kahina Nasri, Koen Norga, Karsten Nysom, Alberto Pappo, Gianluca Rossato, Nicole Scobie, Malcolm Smith, Elliot Stieglitz, Brenda Weigel, Amy Weinstein, Ruth Viana, Dominik Karres, Gilles Vassal |
| Summary: | As the mitogen-activated protein kinase (MAPK) signalling pathway is activated in many paediatric cancers, it is an important therapeutic target. Currently, a range of targeted MAPK pathway inhibitors are being developed in adults. However, MAPK signals through many cascades and feedback loops and perturbing the MAPK pathway may have substantial influence on other pathways as well as normal development. In view of these issues, the ninth Paediatric Strategy Forum focused on MAPK inhibitors. Development of MAPK pathway inhibitors to date has been predominantly driven by adult indications such as malignant melanoma. However, these inhibitors may also target unmet needs in paediatric low-grade gliomas, high-grade gliomas, Langerhans cell histiocytosis, juvenile myelomonocytic leukaemia and several other paediatric conditions. Although MAPK inhibitors have demonstrated activity in paediatric cancer, the response rates and duration of responses needs improvement and better documentation. The rapid development and evaluation of combination approaches, based on a deep understanding of biology, is required to optimise responses and to avoid paradoxical tumour growth and other unintended consequences including severe toxicity. Better inhibitors with higher central nervous systempenetration for primary brain tumours and cancers with a propensity for central nervous system metastases need to be studied to determine if they are more effective than agents currently being used, and the optimum duration of therapy with MAPK inhibition needs to be determined. |
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| Item Description: | Dateiversion vom 3. November 2022 Gesehen am 18.01.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2022.09.036 |