Models of human adamantinomatous craniopharyngioma tissue: Steps toward an effective adjuvant treatment

Abstract

Even though ACP is a benign tumor, treatment is challenging because of the tumor's eloquent location. Today, with the exception of surgical intervention and irradiation, further treatment options are limited. However, ongoing molecular research in this field provides insights into the pathways involved in ACP pathogenesis and reveal a plethora of druggable targets. In the next step, appropriate models are essential to identify the most suitable and effective substances for clinical practice. Primary cell cultures in low passages provide a proper and rapid tool for initial drug potency testing. The patient-derived xenograft (PDX) model accommodates ACP complexity in that it shows respect to the preserved architecture and similar histological appearance to human tumors and therefore provides the most appropriate means for analyzing pharmacological efficacy. Nevertheless, further research is needed to understand in more detail the biological background of ACP pathogenesis, which provides the identification of the best targets in the hierarchy of signaling cascades. ACP models are also important for the continuous testing of new targeting drugs, to establish precision medicine.

Investigating the Protein Signature of Adamantinomatous Craniopharyngioma Pediatric Brain Tumor Tissue: Towards the Comprehension of Its Aggressive Behavior

“…In the same study, the gene ontology enrichment of the AC gene signature classified the majority of them as involved in odontogenic (DLX2, ODAM, AMBN, AMELX, ENAM, TP63, EDAR, SHH, and FGF4), epidermal (including several keratins, KRT5 13-16, 31, 34, and 85, and laminins LAMA3 and LAMC2), and epithelial development. Together with the tumor stem cell markers, CD44 and CD133, AC were found also to express the paracrine factors, BMP4, FGF, and SHH [5]. The downregulation of cell adhesion molecule claudin-1 distinguished AC from other craniopharyngioma subtypes and from the Rathke's cleft benign cysts (RCC) [11].…”

“…The downregulation of cell adhesion molecule claudin-1 distinguished AC from other craniopharyngioma subtypes and from the Rathke's cleft benign cysts (RCC) [11]. On the opposite, the expression of epithelial cell adhesion molecule EpCAM [12] and fascin-1 in the beta-catenin-accumulating cells [5] was found. A transcriptional study on recurrent AC disclosed the upregulation of 16 genes and a significant association of tumor relapse with the expression of CXCL12 and CXCR4 [13].…”

Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology

“…However, recent findings provided a significant insight into the molecular pathogenesis associated with new pharmacological treatment targets and indicated promising radiochemotherapeutic strategies [ 15 – 17 ]. The preclinical testing of these targets in vivo makes suitable models indispensable [ 18 ]. Beside transgenic mouse models, the best conformance in relation to the human ACP was achieved using the intracranial xenograft model established from human tumor tissue [ 19 , 20 , 21 ].…”

“…This includes amongst others the activation of the WNT and EGFR signaling pathway with accompanied gene regulatory capacities, which vary between patients. [ 11 , 17 , 18 , 20 ]. Thus, the PDX model provides a tool for identifying efficient patient specific treatment in the future [ 18 ].…”

“…[ 11 , 17 , 18 , 20 ]. Thus, the PDX model provides a tool for identifying efficient patient specific treatment in the future [ 18 ]. For this purpose, it is of fundamental importance (i) to ensure a sufficient content of vulnerable (vital) tumor proportions before starting extensive treatment testing and (ii) to identify treatment associated changes in a longer course of time due to the relatively slow growth of ACP.…”