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29 results on '"Dolman, Emmy"'

1. Exploring high-throughput drug sensitivity testing in neuroblastoma cell lines and patient-derived tumor organoids in the era of precision medicine

Author

Langenberg, Karin P.S., van Hooff, Sander R., Koopmans, Bianca, Strijker, Josephine G.M., Kholosy, Waleed M., Ober, Kimberley, Zwijnenburg, Danny A., van der Hoek, Jessica J.F., Keller, Kaylee M., Vernooij, Lindy, Schild, Linda G., Looze, Eleonora J., Ebus, Marli E., Essing, Anke H.W., Vree, Paula de, Tas, Michelle L., Matser, Yvette A.H., Wienke, Judith, Volckmann, Richard, Tops, Bastiaan B.J., Kester, Lennart A., Badloe, Shashi, Hehir-Kwa, Jayne Y., Kemmeren, Patrick, Goemans, Bianca F., Zwaan, C. Michel, Oehme, Ina, Jäger, Nathalie, Witt, Olaf, van Eijkelenburg, Natasha K.A., Dierselhuis, Miranda P., Tytgat, Godelieve A.M., Wijnen, Marc H.W., van Noesel, Max M., de Krijger, Ronald R., Eising, Selma, Koster, Jan, Dolman, Emmy M., and Molenaar, Jan J.

Published
2025
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2. Accelerating drug development for neuroblastoma: Summary of the Second Neuroblastoma Drug Development Strategy forum from Innovative Therapies for Children with Cancer and International Society of Paediatric Oncology Europe Neuroblastoma

Author

Moreno, Lucas, Barone, Giuseppe, DuBois, Steven G., Molenaar, Jan, Fischer, Matthias, Schulte, Johannes, Eggert, Angelika, Schleiermacher, Gudrun, Speleman, Frank, Chesler, Louis, Geoerger, Birgit, Hogarty, Michael D., Irwin, Meredith S., Bird, Nick, Blanchard, Guy B., Buckland, Sean, Caron, Hubert, Davis, Susan, De Wilde, Bram, Deubzer, Hedwig E., Dolman, Emmy, Eilers, Martin, George, Rani E., George, Sally, Jaroslav, Štěrba, Maris, John M., Marshall, Lynley, Merchant, Melinda, Mortimer, Peter, Owens, Cormac, Philpott, Anna, Poon, Evon, Shay, Jerry W., Tonelli, Roberto, Valteau-Couanet, Dominique, Vassal, Gilles, Park, Julie R., and Pearson, Andrew D.J.

Published
2020
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3. ALK positively regulates MYCN activity through repression of HBP1 expression

Author

Claeys, Shana, Denecker, Geertrui, Durinck, Kaat, Decaesteker, Bieke, Mus, Liselot M., Loontiens, Siebe, Vanhauwaert, Suzanne, Althoff, Kristina, Wigerup, Caroline, Bexell, Daniel, Dolman, Emmy, Henrich, Kai-Oliver, Wehrmann, Lea, Westerhout, Ellen M., Demoulin, Jean-Baptiste, Kumps, Candy, Van Maerken, Tom, Laureys, Genevieve, Van Neste, Christophe, De Wilde, Bram, De Wever, Olivier, Westermann, Frank, Versteeg, Rogier, Molenaar, Jan J., Påhlman, Sven, Schulte, Johannes H., De Preter, Katleen, and Speleman, Frank

Published
2019
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4. An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity

Author

Calandrini, Camilla, Schutgens, Frans, Oka, Rurika, Margaritis, Thanasis, Candelli, Tito, Mathijsen, Luka, Ammerlaan, Carola, van Ineveld, Ravian L., Derakhshan, Sepide, de Haan, Sanne, Dolman, Emmy, Lijnzaad, Philip, Custers, Lars, Begthel, Harry, Kerstens, Hindrik H. D., Visser, Lindy L., Rookmaaker, Maarten, Verhaar, Marianne, Tytgat, Godelieve A. M., Kemmeren, Patrick, de Krijger, Ronald R., Al-Saadi, Reem, Pritchard-Jones, Kathy, Kool, Marcel, Rios, Anne C., van den Heuvel-Eibrink, Marry M., Molenaar, Jan J., van Boxtel, Ruben, Holstege, Frank C. P., Clevers, Hans, and Drost, Jarno

Published
2020
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8. TBX2 is a neuroblastoma core regulatory circuitry component enhancing MYCN/FOXM1 reactivation of DREAM targets

Author

Decaesteker, Bieke, Denecker, Geertrui, Van Neste, Christophe, Dolman, Emmy M., Van Loocke, Wouter, Gartlgruber, Moritz, Nunes, Carolina, De Vloed, Fanny, Depuydt, Pauline, Verboom, Karen, Rombaut, Dries, Loontiens, Siebe, De Wyn, Jolien, Kholosy, Waleed M., Koopmans, Bianca, Essing, Anke H. W., Herrmann, Carl, Dreidax, Daniel, Durinck, Kaat, Deforce, Dieter, Van Nieuwerburgh, Filip, Henssen, Anton, Versteeg, Rogier, Boeva, Valentina, Schleiermacher, Gudrun, van Nes, Johan, Mestdagh, Pieter, Vanhauwaert, Suzanne, Schulte, Johannes H., Westermann, Frank, Molenaar, Jan J., De Preter, Katleen, and Speleman, Frank

Published
2018
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9. RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition

Author

Nunes, Carolina, primary, Depestel, Lisa, additional, Mus, Liselot, additional, Keller, Kaylee M., additional, Delhaye, Louis, additional, Louwagie, Amber, additional, Rishfi, Muhammad, additional, Whale, Alex, additional, Kara, Neesha, additional, Andrews, Simon R., additional, Dela Cruz, Filemon, additional, You, Daoqi, additional, Siddiquee, Armaan, additional, Cologna, Camila Takeno, additional, De Craemer, Sam, additional, Dolman, Emmy, additional, Bartenhagen, Christoph, additional, De Vloed, Fanny, additional, Sanders, Ellen, additional, Eggermont, Aline, additional, Bekaert, Sarah-Lee, additional, Van Loocke, Wouter, additional, Bek, Jan Willem, additional, Dewyn, Givani, additional, Loontiens, Siebe, additional, Van Isterdael, Gert, additional, Decaesteker, Bieke, additional, Tilleman, Laurentijn, additional, Van Nieuwerburgh, Filip, additional, Vermeirssen, Vanessa, additional, Van Neste, Christophe, additional, Ghesquiere, Bart, additional, Goossens, Steven, additional, Eyckerman, Sven, additional, De Preter, Katleen, additional, Fischer, Matthias, additional, Houseley, Jon, additional, Molenaar, Jan, additional, De Wilde, Bram, additional, Roberts, Stephen S., additional, Durinck, Kaat, additional, and Speleman, Frank, additional

Published
2022
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11. RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition

Author

Nunes, Carolina, Depestel, Lisa, Mus, Liselot, Keller, Kaylee M., Delhaye, Louis, Louwagie, Amber, Rishfi, Muhammad, Whale, Alex, Kara, Neesha, Andrews, Simon R., Cruz, Filemon Dela, You, Daoqi, Siddiquee, Armaan, Cologna, Camila Takeno, De Craemer, Sam, Dolman, Emmy, Bartenhagen, Christoph, De Vloed, Fanny, Sanders, Ellen, Eggermont, Aline, Bekaert, Sarah Lee, Van Loocke, Wouter, Bek, Jan Willem, Dewyn, Givani, Loontiens, Siebe, Van Isterdael, Gert, Decaesteker, Bieke, Tilleman, Laurentijn, Van Nieuwerburgh, Filip, Vermeirssen, Vanessa, Van Neste, Christophe, Ghesquiere, Bart, Goossens, Steven, Eyckerman, Sven, De Preter, Katleen, Fischer, Matthias, Houseley, Jon, Molenaar, Jan, De Wilde, Bram, Roberts, Stephen S., Durinck, Kaat, Speleman, Frank, Nunes, Carolina, Depestel, Lisa, Mus, Liselot, Keller, Kaylee M., Delhaye, Louis, Louwagie, Amber, Rishfi, Muhammad, Whale, Alex, Kara, Neesha, Andrews, Simon R., Cruz, Filemon Dela, You, Daoqi, Siddiquee, Armaan, Cologna, Camila Takeno, De Craemer, Sam, Dolman, Emmy, Bartenhagen, Christoph, De Vloed, Fanny, Sanders, Ellen, Eggermont, Aline, Bekaert, Sarah Lee, Van Loocke, Wouter, Bek, Jan Willem, Dewyn, Givani, Loontiens, Siebe, Van Isterdael, Gert, Decaesteker, Bieke, Tilleman, Laurentijn, Van Nieuwerburgh, Filip, Vermeirssen, Vanessa, Van Neste, Christophe, Ghesquiere, Bart, Goossens, Steven, Eyckerman, Sven, De Preter, Katleen, Fischer, Matthias, Houseley, Jon, Molenaar, Jan, De Wilde, Bram, Roberts, Stephen S., Durinck, Kaat, and Speleman, Frank

Abstract

High-risk neuroblastoma, a pediatric tumor originating from the sympathetic nervous system, has a low mutation load but highly recurrent somatic DNA copy number variants. Previously, segmental gains and/or amplifications allowed identification of drivers for neuroblastoma development. Using this approach, combined with gene dosage impact on expression and survival, we identified ribonucleotide reductase subunit M2 (RRM2) as a candidate dependency factor further supported by growth inhibition upon in vitro knockdown and accelerated tumor formation in a neuroblastoma zebrafish model coexpressing human RRM2 with MYCN. Forced RRM2 induction alleviates excessive replicative stress induced by CHK1 inhibition, while high RRM2 expression in human neuroblastomas correlates with high CHK1 activity. MYCN-driven zebrafish tumors with RRM2 co-overexpression exhibit differentially expressed DNA repair genes in keeping with enhanced ATR-CHK1 signaling activity. In vitro, RRM2 inhibition enhances intrinsic replication stress checkpoint addiction. Last, combinatorial RRM2-CHK1 inhibition acts synergistic in high-risk neuroblastoma cell lines and patient-derived xenograft models, illustrating the therapeutic potential.

Published
2022

12. RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition

Author

Afd Pharmaceutics, Pharmaceutics, Nunes, Carolina, Depestel, Lisa, Mus, Liselot, Keller, Kaylee M., Delhaye, Louis, Louwagie, Amber, Rishfi, Muhammad, Whale, Alex, Kara, Neesha, Andrews, Simon R., Cruz, Filemon Dela, You, Daoqi, Siddiquee, Armaan, Cologna, Camila Takeno, De Craemer, Sam, Dolman, Emmy, Bartenhagen, Christoph, De Vloed, Fanny, Sanders, Ellen, Eggermont, Aline, Bekaert, Sarah Lee, Van Loocke, Wouter, Bek, Jan Willem, Dewyn, Givani, Loontiens, Siebe, Van Isterdael, Gert, Decaesteker, Bieke, Tilleman, Laurentijn, Van Nieuwerburgh, Filip, Vermeirssen, Vanessa, Van Neste, Christophe, Ghesquiere, Bart, Goossens, Steven, Eyckerman, Sven, De Preter, Katleen, Fischer, Matthias, Houseley, Jon, Molenaar, Jan, De Wilde, Bram, Roberts, Stephen S., Durinck, Kaat, Speleman, Frank, Afd Pharmaceutics, Pharmaceutics, Nunes, Carolina, Depestel, Lisa, Mus, Liselot, Keller, Kaylee M., Delhaye, Louis, Louwagie, Amber, Rishfi, Muhammad, Whale, Alex, Kara, Neesha, Andrews, Simon R., Cruz, Filemon Dela, You, Daoqi, Siddiquee, Armaan, Cologna, Camila Takeno, De Craemer, Sam, Dolman, Emmy, Bartenhagen, Christoph, De Vloed, Fanny, Sanders, Ellen, Eggermont, Aline, Bekaert, Sarah Lee, Van Loocke, Wouter, Bek, Jan Willem, Dewyn, Givani, Loontiens, Siebe, Van Isterdael, Gert, Decaesteker, Bieke, Tilleman, Laurentijn, Van Nieuwerburgh, Filip, Vermeirssen, Vanessa, Van Neste, Christophe, Ghesquiere, Bart, Goossens, Steven, Eyckerman, Sven, De Preter, Katleen, Fischer, Matthias, Houseley, Jon, Molenaar, Jan, De Wilde, Bram, Roberts, Stephen S., Durinck, Kaat, and Speleman, Frank

Published
2022

13. Neuroblastoma and DIPG Organoid Coculture System for Personalized Assessment of Novel Anticancer Immunotherapies

Author

M Kholosy, Waleed, Derieppe, Marc, van den Ham, Femke, Ober, Kim, Su, Yan, Custers, Lars, Schild, Linda, M J van Zogchel, Lieke, M Wellens, Lianne, R Ariese, Hendrikus, Szanto, Celina L, Wienke, Judith, Dierselhuis, Miranda P, van Vuurden, Dannis, Dolman, Emmy M, Molenaar, Jan J, Afd Pharmaceutics, Pharmaceutics, Afd Pharmaceutics, and Pharmaceutics

Subjects
cancer immunotherapy, medicine.drug_class, business.industry, medicine.medical_treatment, Medicine (miscellaneous), Dinutuximab, Immunotherapy, Monoclonal antibody, medicine.disease, Article, neuroblastoma, Immune system, paediatric cancer organoids, Cancer immunotherapy, diffuse intrinsic pontine glioma (DIPG), Neuroblastoma, coculture system, Cancer research, medicine, Organoid, Medicine, business, Ex vivo
Abstract

Cancer immunotherapy has transformed the landscape of adult cancer treatment and holds a great promise to treat paediatric malignancies. However, in vitro test coculture systems to evaluate the efficacy of immunotherapies on representative paediatric tumour models are lacking. Here, we describe a detailed procedure for the establishment of an ex vivo test coculture system of paediatric tumour organoids and immune cells that enables assessment of different immunotherapy approaches in paediatric tumour organoids. We provide a step-by-step protocol for an efficient generation of patient-derived diffuse intrinsic pontine glioma (DIPG) and neuroblastoma organoids stably expressing eGFP-ffLuc transgenes using defined serum-free medium. In contrast to the chromium-release assay, the new platform allows for visualization, monitoring and robust quantification of tumour organoid cell cytotoxicity using a non-radioactive assay in real-time. To evaluate the utility of this system for drug testing in the paediatric immuno-oncology field, we tested our in vitro assay using a clinically used immunotherapy strategy for children with high-risk neuroblastoma, dinutuximab (anti-GD2 monoclonal antibody), on GD2 proficient and deficient patient-derived neuroblastoma organoids. We demonstrated the feasibility and sensitivity of our ex vivo coculture system using human immune cells and paediatric tumour organoids as ex vivo tumour models. Our study provides a novel platform for personalized testing of potential anticancer immunotherapies for aggressive paediatric cancers such as neuroblastoma and DIPG.

Published
2021

16. Neuroblastoma and DIPG Organoid Coculture System for Personalized Assessment of Novel Anticancer Immunotherapies

Author

Afd Pharmaceutics, Pharmaceutics, M Kholosy, Waleed, Derieppe, Marc, van den Ham, Femke, Ober, Kim, Su, Yan, Custers, Lars, Schild, Linda, M J van Zogchel, Lieke, M Wellens, Lianne, R Ariese, Hendrikus, Szanto, Celina L, Wienke, Judith, Dierselhuis, Miranda P, van Vuurden, Dannis, Dolman, Emmy M, Molenaar, Jan J, Afd Pharmaceutics, Pharmaceutics, M Kholosy, Waleed, Derieppe, Marc, van den Ham, Femke, Ober, Kim, Su, Yan, Custers, Lars, Schild, Linda, M J van Zogchel, Lieke, M Wellens, Lianne, R Ariese, Hendrikus, Szanto, Celina L, Wienke, Judith, Dierselhuis, Miranda P, van Vuurden, Dannis, Dolman, Emmy M, and Molenaar, Jan J

Published
2021

18. RRM2 is a target for synthetic lethal interactions with replication stress checkpoint addiction in high-risk neuroblastoma

Author

Nunes, Carolina, primary, Depestel, Lisa, additional, Mus, Liselot, additional, Keller, Kaylee, additional, Delhaye, Louis, additional, Louwagie, Amber, additional, Rishfi, Muhammad, additional, Dolman, Emmy, additional, Olexiouk, Volodimir, additional, Bartenhagen, Christoph, additional, De Vloed, Fanny, additional, Sanders, Ellen, additional, Eggermont, Aline, additional, Van Laere, Jolien, additional, Desmet, Els, additional, Van Loocke, Wouter, additional, Morscio, Julie, additional, Loontiens, Siebe, additional, Depuydt, Pauline, additional, Decaesteker, Bieke, additional, Tilleman, Laurentijn, additional, Van Nieuwerburgh, Filip, additional, Deforce, Dieter, additional, De Wilde, Bram, additional, Van Vlierberghe, Pieter, additional, Vermeirssen, Vanessa, additional, Goossens, Steven, additional, Eyckerman, Sven, additional, Van Neste, Christophe, additional, Roberts, Stephen, additional, Fischer, Matthias, additional, Molenaar, Jan, additional, Durinck, Kaat, additional, and Speleman, Frank, additional

Published
2020
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21. An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity

Author

UU BETA RESEARCH, Faculteit Diergeneeskunde, Calandrini, Camilla, Schutgens, Frans, Oka, Rurika, Margaritis, Thanasis, Candelli, Tito, Mathijsen, Luka, Ammerlaan, Carola, van Ineveld, Ravian L, Derakhshan, Sepide, de Haan, Sanne, Dolman, Emmy, Lijnzaad, Philip, Custers, Lars, Begthel, Harry, Kerstens, Hindrik H D, Visser, Lindy L, Rookmaaker, Maarten, Verhaar, Marianne, Tytgat, Godelieve A M, Kemmeren, Patrick, de Krijger, Ronald R, Al-Saadi, Reem, Pritchard-Jones, Kathy, Kool, Marcel, Rios, Anne C, van den Heuvel-Eibrink, Marry M, Molenaar, Jan J, van Boxtel, Ruben, Holstege, Frank C P, Clevers, Hans, Drost, Jarno, UU BETA RESEARCH, Faculteit Diergeneeskunde, Calandrini, Camilla, Schutgens, Frans, Oka, Rurika, Margaritis, Thanasis, Candelli, Tito, Mathijsen, Luka, Ammerlaan, Carola, van Ineveld, Ravian L, Derakhshan, Sepide, de Haan, Sanne, Dolman, Emmy, Lijnzaad, Philip, Custers, Lars, Begthel, Harry, Kerstens, Hindrik H D, Visser, Lindy L, Rookmaaker, Maarten, Verhaar, Marianne, Tytgat, Godelieve A M, Kemmeren, Patrick, de Krijger, Ronald R, Al-Saadi, Reem, Pritchard-Jones, Kathy, Kool, Marcel, Rios, Anne C, van den Heuvel-Eibrink, Marry M, Molenaar, Jan J, van Boxtel, Ruben, Holstege, Frank C P, Clevers, Hans, and Drost, Jarno

Published
2020

22. Accelerating drug development for neuroblastoma: Summary of the Second Neuroblastoma Drug Development Strategy forum from Innovative Therapies for Children with Cancer and International Society of Paediatric Oncology Europe Neuroblastoma

Author

UU BETA RESEARCH, Moreno, Lucas, Barone, Giuseppe, DuBois, Steven G, Molenaar, Jan, Fischer, Matthias, Schulte, Johannes, Eggert, Angelika, Schleiermacher, Gudrun, Speleman, Frank, Chesler, Louis, Geoerger, Birgit, Hogarty, Michael D, Irwin, Meredith S, Bird, Nick, Blanchard, Guy B, Buckland, Sean, Caron, Hubert, Davis, Susan, De Wilde, Bram, Deubzer, Hedwig E, Dolman, Emmy, Eilers, Martin, George, Rani E, George, Sally, Jaroslav, Štěrba, Maris, John M, Marshall, Lynley, Merchant, Melinda, Mortimer, Peter, Owens, Cormac, Philpott, Anna, Poon, Evon, Shay, Jerry W, Tonelli, Roberto, Valteau-Couanet, Dominique, Vassal, Gilles, Park, Julie R, Pearson, Andrew D J, UU BETA RESEARCH, Moreno, Lucas, Barone, Giuseppe, DuBois, Steven G, Molenaar, Jan, Fischer, Matthias, Schulte, Johannes, Eggert, Angelika, Schleiermacher, Gudrun, Speleman, Frank, Chesler, Louis, Geoerger, Birgit, Hogarty, Michael D, Irwin, Meredith S, Bird, Nick, Blanchard, Guy B, Buckland, Sean, Caron, Hubert, Davis, Susan, De Wilde, Bram, Deubzer, Hedwig E, Dolman, Emmy, Eilers, Martin, George, Rani E, George, Sally, Jaroslav, Štěrba, Maris, John M, Marshall, Lynley, Merchant, Melinda, Mortimer, Peter, Owens, Cormac, Philpott, Anna, Poon, Evon, Shay, Jerry W, Tonelli, Roberto, Valteau-Couanet, Dominique, Vassal, Gilles, Park, Julie R, and Pearson, Andrew D J

Published
2020

23. An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity

Author

Nefro Vasculaire Geneeskunde, Groep Holstege, CMM Groep Klumperman, MS Nefrologie, Regenerative Medicine and Stem Cells, Circulatory Health, Pathologie Groep Blokx, Pathologie Pathologen staf, Child Health, CMM Groep Cuppen, Cancer, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Calandrini, Camilla, Schutgens, Frans, Oka, Rurika, Margaritis, Thanasis, Candelli, Tito, Mathijsen, Luka, Ammerlaan, Carola, van Ineveld, Ravian L., Derakhshan, Sepide, de Haan, Sanne, Dolman, Emmy, Lijnzaad, Philip, Custers, Lars, Begthel, Harry, Kerstens, Hindrik H.D., Visser, Lindy L., Rookmaaker, Maarten, Verhaar, Marianne, Tytgat, Godelieve A.M., Kemmeren, Patrick, de Krijger, Ronald R., Al-Saadi, Reem, Pritchard-Jones, Kathy, Kool, Marcel, Rios, Anne C., van den Heuvel-Eibrink, Marry M., Molenaar, Jan J., van Boxtel, Ruben, Holstege, Frank C.P., Clevers, Hans, Drost, Jarno, Nefro Vasculaire Geneeskunde, Groep Holstege, CMM Groep Klumperman, MS Nefrologie, Regenerative Medicine and Stem Cells, Circulatory Health, Pathologie Groep Blokx, Pathologie Pathologen staf, Child Health, CMM Groep Cuppen, Cancer, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Calandrini, Camilla, Schutgens, Frans, Oka, Rurika, Margaritis, Thanasis, Candelli, Tito, Mathijsen, Luka, Ammerlaan, Carola, van Ineveld, Ravian L., Derakhshan, Sepide, de Haan, Sanne, Dolman, Emmy, Lijnzaad, Philip, Custers, Lars, Begthel, Harry, Kerstens, Hindrik H.D., Visser, Lindy L., Rookmaaker, Maarten, Verhaar, Marianne, Tytgat, Godelieve A.M., Kemmeren, Patrick, de Krijger, Ronald R., Al-Saadi, Reem, Pritchard-Jones, Kathy, Kool, Marcel, Rios, Anne C., van den Heuvel-Eibrink, Marry M., Molenaar, Jan J., van Boxtel, Ruben, Holstege, Frank C.P., Clevers, Hans, and Drost, Jarno

Published
2020

24. ALK positively regulates MYCN activity through repression of HBP1 expression

Author

Claeys, Shana, primary, Denecker, Geertrui, additional, Durinck, Kaat, additional, Decaesteker, Bieke, additional, Mus, Liselot M., additional, Loontiens, Siebe, additional, Vanhauwaert, Suzanne, additional, Althoff, Kristina, additional, Wigerup, Caroline, additional, Bexell, Daniel, additional, Dolman, Emmy, additional, Henrich, Kai-Oliver, additional, Wehrmann, Lea, additional, Westerhout, Ellen M., additional, Demoulin, Jean-Baptiste, additional, Kumps, Candy, additional, Van Maerken, Tom, additional, Laureys, Genevieve, additional, Van Neste, Christophe, additional, De Wilde, Bram, additional, De Wever, Olivier, additional, Westermann, Frank, additional, Versteeg, Rogier, additional, Molenaar, Jan J., additional, Påhlman, Sven, additional, Schulte, Johannes H., additional, De Preter, Katleen, additional, and Speleman, Frank, additional

Published
2018
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25. Anti-GD2 Immunoliposomes for Targeted Delivery of the Survivin Inhibitor Sepantronium Bromide (YM155) to Neuroblastoma Tumor Cells

Author

Afd Pharmacoepi & Clinical Pharmacology, Afd Chemical Biology and Drug Discovery, Afd Pharmaceutics, Pharmacoepidemiology and Clinical Pharmacology, Pharmaceutics, Chemical Biology and Drug Discovery, Gholizadeh, Shima, Dolman, Emmy M., Wieriks, Rebecca, Sparidans, Rolf W., Hennink, Wim E., Kok, Robbert J., Afd Pharmacoepi & Clinical Pharmacology, Afd Chemical Biology and Drug Discovery, Afd Pharmaceutics, Pharmacoepidemiology and Clinical Pharmacology, Pharmaceutics, Chemical Biology and Drug Discovery, Gholizadeh, Shima, Dolman, Emmy M., Wieriks, Rebecca, Sparidans, Rolf W., Hennink, Wim E., and Kok, Robbert J.

Published
2018

27. Accelerating drug development for neuroblastoma: Summary of the Second Neuroblastoma Drug Development Strategy forum from Innovative Therapies for Children with Cancer and International Society of Paediatric Oncology Europe Neuroblastoma

Author

Moreno, Lucas, Barone, Giuseppe, DuBois, Steven G, Molenaar, Jan, Fischer, Matthias, Schulte, Johannes, Eggert, Angelika, Schleiermacher, Gudrun, Speleman, Frank, Chesler, Louis, Geoerger, Birgit, Hogarty, Michael D, Irwin, Meredith S, Bird, Nick, Blanchard, Guy B, Buckland, Sean, Caron, Hubert, Davis, Susan, De Wilde, Bram, Deubzer, Hedwig E, Dolman, Emmy, Eilers, Martin, George, Rani E, George, Sally, Jaroslav, Štěrba, Maris, John M, Marshall, Lynley, Merchant, Melinda, Mortimer, Peter, Owens, Cormac, Philpott, Anna, Poon, Evon, Shay, Jerry W, Tonelli, Roberto, Valteau-Couanet, Dominique, Vassal, Gilles, Park, Julie R, and Pearson, Andrew DJ

Subjects
Brain Neoplasms, Therapies, Investigational, Preclinical testing, Drug development, Antineoplastic Agents, Congresses as Topic, Medical Oncology, Pediatrics, 3. Good health, Europe, Neuroblastoma, Clinical trials, Phase I, MYCN, Drug Discovery, Humans, Epigenetics, Molecular Targeted Therapy, Child, Protein Kinase Inhibitors
Abstract

Only one class of targeted agents (anti-GD2 antibodies) has been incorporated into front-line therapy for neuroblastoma since the 1980s. The Neuroblastoma New Drug Development Strategy (NDDS) initiative commenced in 2012 to accelerate the development of new drugs for neuroblastoma. Advances have occurred, with eight of nine high-priority targets being evaluated in paediatric trials including anaplastic lymphoma kinase inhibitors being investigated in front-line, but significant challenges remain. This article reports the conclusions of the second NDDS forum, which expanded across the Atlantic to further develop the initiative. Pre-clinical and clinical data for 40 genetic targets and mechanisms of action were prioritised and drugs were identified for early-phase trials. Strategies to develop drugs targeting TERT, telomere maintenance, ATRX, alternative lengthening of telomeres (ALT), BRIP1 and RRM2 as well as direct targeting of MYCN are high priority and should be championed for drug discovery. Promising pre-clinical data suggest that targeting of ALT by ATM or PARP inhibition may be potential strategies. Drugs targeting CDK2/9, CDK7, ATR and telomere maintenance should enter paediatric clinical development rapidly. Optimising the response to anti-GD2 by combinations with chemotherapy, targeted agents and other immunological targets are crucial. Delivering this strategy in the face of small patient cohorts, genomically defined subpopulations and a large number of permutations of combination trials, demands even greater international collaboration. In conclusion, the NDDS provides an internationally agreed, biologically driven selection of prioritised genetic targets and drugs. Improvements in the strategy for conducting trials in neuroblastoma will accelerate bringing these new drugs more rapidly to front-line therapy.

28. The HBP1 tumour suppressor is a negative epigenetic regulator of MYCN-driven neuroblastoma through interaction with the PRC2 complex

Author

Shana Claeys, Geertrui Denecker, Bieke Decaesteker, Janssens, Els, Kumps, Candy, Brouwer, Sara, Lambertz, Irina, Fieuw, Annelies, Suzanne Vanhauwaert, Althoff, Kristina, Bate-Eya, Laurel, Dolman, Emmy, Wigerup, Caroline, Bexell, Daniel, Pahlman, Sven, Henrich, Ko, Wehrmann, Lea, Hogarty, Md, Demoulin, Jean-Baptiste, Tom Van Maerken, Laureys, Genevieve, Christophe Van Neste, Bram De Wilde, Kaat Durinck, Westermann, Frank, Schulte, Johannes, Katleen De Preter, and Frank Speleman

29. Towards Targeted Treatment for Pediatric Cancer: Inhibition of the replication stress response as a novel therapeutic approach

Author

Keller, Kaylee Marie, Faculteit Betawetenschappen, Molenaar, Jan, van Hooff, Sander Roeland, Dolman, Emmy, and University Utrecht

Subjects
replicatiestress, kinderkanker, replication stress, checkpoint kinase 1, PARP, preklinisch onderzoek, synergy, DNA repair, pediatric cancer, PARP, synergie, DNA-schade, DNA-reparatie, DNA damage, preclinical research
Abstract

Decades of data support replication stress as a therapeutic target, however, toxic side effects often encountered during chemotherapy treatment and long-term health consequences often limit the practical applicability of these compounds. With the advent of small molecule inhibitors, a more targeted and possibly less toxic approach to treating pediatric solid malignancies has emerged. In chapter 2 of this thesis, we conduct a Target Actionability Review (TAR) to evaluate specific targets within the replication stress response. The TAR methodology aims to match targeted anti-cancer drugs with specific cancer subtypes based on preclinical studies. In our study, we create a comprehensive, structured, and critically evaluated overview of literature related to targeting replication stress in pediatric solid malignancies. In addition, we underscore the importance of robust preclinical studies and highlight emerging targets such as PARP, which is explored in more detail in chapter 3. The development of novel therapeutic approaches for pediatric cancer is often challenged by the fact that there are very few patients available to participate in clinical studies. Not only does this create a certain degree of hesitancy to fund pediatric-specific (pre)clinical drug development, but the execution of robust clinical trials also remains difficult. The existence of a drug target applicable in a wider range of tumor types could help mitigate these challenges and aid in the development of safe therapeutics for children with cancer. In chapter 3 PARP is explored as a broader pediatric target and potential biomarkers and therapeutic combinations are suggested. In the remaining chapters of this thesis, we dive deeper into targeting replication stress and investigate CHK1 as a therapeutic target in neuroblastoma. Neuroblastoma is a malignancy of the sympathetic nervous system and is the most common extracranial solid tumor found in children. Although most high-risk neuroblastoma tumors initially respond to treatment, relapse and therapy resistance remain major clinical obstacles. Approximately 50% of high-risk patients eventually succumb to the disease, thus there is an absolute need for more effective therapeutic approaches for these patients. While neuroblastoma is characterized by a paucity in targetable somatic mutations, a remarkable number of tumors are driven by chromosomal aberrations such as hemizygous loss of chromosome 11q or amplification of MYCN. Although these abnormalities are very different from one another on a genomic level, they both induce replication stress, offering a targetable vulnerability. In chapter 4, we establish chromosome 11q loss and MYCN amplification as therapeutic biomarkers for CHK1 inhibition and in chapter 5 we elucidate the mechanism driving CHK1 inhibitor sensitivity in MYCN amplified neuroblastoma. Additionally, both chapters propose novel therapeutic combinations that could extend the clinical applicability of CHK1 inhibition in neuroblastoma. Lastly, in chapter 6, we discuss our main findings and their future implications. Altogether, the discussion highlights our insights and brings our findings into context with other published research with the hope of helping the development of safe and effective therapeutics for children with cancer.

Published
2023

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