Adamantinomatous craniopharyngioma in the molecular age and the potential of targeted therapies: a review
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INVITED PAPER
Adamantinomatous craniopharyngioma in the molecular age and the potential of targeted therapies: a review Ros Whelan 1
&
Astrid Hengartner 1,2 & Zach Folzenlogen 1 & Eric Prince 1,2,3 & Todd C. Hankinson 1,2,3
Received: 7 May 2020 / Accepted: 11 May 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Pediatric adamantinomatous craniopharyngiomas (ACPs) are histologically benign brain tumors that often follow an aggressive clinical course. Arising in the sellar/suprasellar region, they grow in close proximity to critical neurological and vascular structures and can result in significant neuroendocrine morbidity. First-line treatment often involves surgical resection with or without radiotherapy and has been associated with significant morbidity and poor quality of life outcomes. As a result, the discovery of alternative effective and safe treatments is clearly desirable. In recent years, laboratory studies have harnessed sophisticated techniques to identify the upregulation of several markers that may represent potential therapeutic targets. These targets include IL-6, PD1/PD-L1, MEK, IDO-1, and others. Agents that target these pathways exist, and there is an opportunity to investigate their potential efficacy in the treatment of ACP. Trials investigating some of these agents as monotherapy and in combination for the treatment of pediatric ACP are underway or in development. If positive, these trials may result in a paradigm shift in treatment that will hopefully result in reduced morbidity and better outcomes for patients. Keywords Craniopharyngioma . Childhood craniopharyngioma . IL-6 inhibition . PD-1 inhibition . Checkpoint inhibition . MEK inhibition . Senescence
Introduction Pediatric adamantinomatous craniopharyngioma (ACP) is a histologically benign brain tumor that, due to its aggressive clinical course, can result in reduced lifespan and significant morbidity [1–3]. Likely related to the tumors benign histology and relative rarity (~ 1.9 cases/million patient years [4]), novel therapies for ACP have been elusive, and medications specifically engineered to combat ACP are unlikely to be developed. As a result, novel
* Ros Whelan [email protected] Eric Prince [email protected] Todd C. Hankinson [email protected] 1
Department of Neurosurgery, University of Colorado Hospital, Aurora, CO, USA
2
Division of Pediatric neurosurgery, Children’s Hospital Colorado, University of Colorado, Aurora, CO, USA
3
Morgan Adams Foundation Pediatric Brain Tumor Program, Aurora, CO, USA
therapy for patients with ACP will need to arise from improved understanding of the tumors biology, with correlation of this knowledge to potential existing therapeutic agents. ACP originates in the sellar/suprasellar region, likely developing from remnants of Rathke’s pouch. Radiographically, these tumors appear as mixed solid and cystic lesions, often with areas of calcification (Fig. 1a and b). Histologically, ACPs are heterogeneous tumors that bare some rese
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