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Targeting tachykinin receptors in neuroblastoma

(2017) ONCOTARGET. 8(1). p.430-443
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Abstract
Neuroblastoma is the most common extracranial tumor in children. Despite aggressive multimodal treatment, high-risk neuroblastoma remains a clinical challenge with survival rates below 50%. Adding targeted drugs to first-line therapy regimens is a promising approach to improve survival in these patients. TACR1 activation by substance P has been reported to be mitogenic in cancer cell lines. Tachykinin receptor (TACR1) antagonists are approved for clinical use as an antiemetic remedy since 2003. Tachykinin receptor inhibition has recently been shown to effectively reduce growth of several tumor types. Here, we report that neuroblastoma cell lines express TACR1, and that targeting TACR1 activity significantly reduced cell viability and induced apoptosis in neuroblastoma cell lines. Gene expression profiling revealed that TACR1 inhibition repressed E2F2 and induced TP53 signaling. Treating mice harboring established neuroblastoma xenograft tumors with Aprepitant also significantly reduced tumor burden. Thus, we provide evidence that the targeted inhibition of tachykinin receptor signaling shows therapeutic efficacy in preclinical models for high-risk neuroblastoma.
Keywords
fosaprepitant, aprepitant, neuroblastoma, NK1R, targeted therapy, SUBSTANCE-P, NEUROKININ-1 RECEPTOR, ANTAGONIST APREPITANT, CELL LINES, APOPTOSIS, BIOCONDUCTOR, EXPRESSION, PATHWAYS, GROWTH, NK-1

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Chicago
Henssen, Anton G, Andrea Odersky, Annabell Szymansky, Marleen Seiler, Kristina Althoff, Anneleen Beckers, Franki Speleman, et al. 2017. “Targeting Tachykinin Receptors in Neuroblastoma.” Oncotarget 8 (1): 430–443.
APA
Henssen, A. G., Odersky, A., Szymansky, A., Seiler, M., Althoff, K., Beckers, A., Speleman, F., et al. (2017). Targeting tachykinin receptors in neuroblastoma. ONCOTARGET, 8(1), 430–443.
Vancouver
1.
Henssen AG, Odersky A, Szymansky A, Seiler M, Althoff K, Beckers A, et al. Targeting tachykinin receptors in neuroblastoma. ONCOTARGET. 2017;8(1):430–43.
MLA
Henssen, Anton G, Andrea Odersky, Annabell Szymansky, et al. “Targeting Tachykinin Receptors in Neuroblastoma.” ONCOTARGET 8.1 (2017): 430–443. Print.
@article{8510877,
  abstract     = {Neuroblastoma is the most common extracranial tumor in children. Despite aggressive multimodal treatment, high-risk neuroblastoma remains a clinical challenge with survival rates below 50\%. Adding targeted drugs to first-line therapy regimens is a promising approach to improve survival in these patients. TACR1 activation by substance P has been reported to be mitogenic in cancer cell lines. Tachykinin receptor (TACR1) antagonists are approved for clinical use as an antiemetic remedy since 2003. Tachykinin receptor inhibition has recently been shown to effectively reduce growth of several tumor types. Here, we report that neuroblastoma cell lines express TACR1, and that targeting TACR1 activity significantly reduced cell viability and induced apoptosis in neuroblastoma cell lines. Gene expression profiling revealed that TACR1 inhibition repressed E2F2 and induced TP53 signaling. Treating mice harboring established neuroblastoma xenograft tumors with Aprepitant also significantly reduced tumor burden. Thus, we provide evidence that the targeted inhibition of tachykinin receptor signaling shows therapeutic efficacy in preclinical models for high-risk neuroblastoma.},
  author       = {Henssen, Anton G and Odersky, Andrea and Szymansky, Annabell and Seiler, Marleen and Althoff, Kristina and Beckers, Anneleen and Speleman, Franki and Sch{\"a}fers, Simon and De Preter, Katleen and Astrahanseff, Kathy and Struck, Joachim and Schramm, Alexander and Eggert, Angelika and Bergmann, Andreas and Schulte, Johannes H},
  issn         = {1949-2553},
  journal      = {ONCOTARGET},
  language     = {eng},
  number       = {1},
  pages        = {430--443},
  title        = {Targeting tachykinin receptors in neuroblastoma},
  url          = {http://dx.doi.org/10.18632/oncotarget.13440},
  volume       = {8},
  year         = {2017},
}

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