Molecular pathogenesis of craniopharyngioma: switching from a surgical approach to a biological one

Abstract

<jats:p>Craniopharyngioma has long been considered a benign tumor because of its pathological aspect. This primordial view of craniopharyngioma fit with the primitive treatment attempts based on blind resection of the tumor each time it recurred. The limits of this management strategy were proven early by the high morbidity related to the resection and recurrence risk despite radical lesion removal. Nowadays, craniopharyngioma must be considered a complex molecular disease, and a detailed explanation of the mechanisms underlying its aggressive biological and clinical behavior, despite some benign pathological features, would be the first step toward defining the best management of craniopharyngioma. Indeed, advances in the knowledge of the molecular mechanisms at the base of craniopharyngioma oncogenesis will lead to comprehension of the critical checkpoints involved in neoplastic transformation. The final research target will be the definition of new biological agents able to reverse the neoplastic process by acting on these critical checkpoints. This biological approach will lead to a refined therapy combining higher efficacy and safety with lower morbidity. In this paper the authors reveal state-of-the-art comprehension of the molecular biology of craniopharyngioma and the consequent therapeutic implications.</jats:p>

Molecular oncogenesis of craniopharyngioma: current and future strategies for the development of targeted therapies

“…1). 35,38,48,54,68,71,87 Thus, the intracellular b-catenin balance plays an important role in not only embryogenesis, but tumorigenesis as well.…”

“…51 The underexpression of MIF in rapidly recurring tumors is counterintuitive, whereas underexpression of galectin-3 suggests dysfunction in the elimination of embryonal tissues that cause craniopharyngiomas to form in the first place. 51,68 Proteases and transcriptional regulators under the control of these inflammatory cytokines also demonstrate unusual patterns in recurrent tumors, such that cathepsins and retinoic acid receptor (RAR) expression are dependent on the specific isoform affected.…”

Proteomics in pediatric cystic craniopharyngioma

“…As a result, the decrease of α‐defensins in the post‐treatment period may account for the reduced fluid production and the cyst shrinkage. IFN‐α may reduce α‐defensin levels through an antitumoral effect on the squamous epithelial cells, an immuno‐modulatory action on the recruitment of inflammatory cells, and anti‐angiogenic activity . The high levels of α‐defensins in ACP cystic fluid indicate no blood barrier disruption for the cyst formation since the serum levels of α‐defensins is very low.…”

Surgery of Craniopharyngiomas in Children

“…There is no conclusive evidence to support genetic alterations in craniopharyngiomas that can serve as reliable molecular markers in craniopharyngiomas (Pettorini et al, 2010;Hussain et al, 2013). While Reinstein et al documented nonrandom genetic alterations and possibly activation of oncogenes located in defined chromosomal regions (Rienstein et al, 2003), Yashimoto and his co-workers posit that the identified genomic alterations in adamantinomatous craniopharyngiomas do not contribute to tumorigenesis (Yoshimoto et al, 2004).…”