In order to develop robust in vivo drug testing methodology, the murine orthotopic craniopharyngioma model (PDX) was characterized by magnetic resonance imaging (MRI) and histology in xenografts from three patients (ACP1-3).
Mean expression levels (recurrent craniopharyngiomas compared with non-recurrent craniopharyngiomas, as normalized to expression of β-actin) were 3.09 versus 0.75 (P = 0.001) for HIF-1α, 1.07 versus 0.32 (P = 0.000) for VEGF, 1.21 versus 1.93 (P = 0.503) for CA9.
The level of white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet, albumin, neutrophil lymphocyte ratio (NLR), derived NLR (dNLR), platelet lymphocyte ratio (PLR), monocyte lymphocyte ratio (MLR) and prognostic nutritional index (PNI) were compared between the CP and other sellar region tumors.
In this study, we measured the immunohistochemical expression of β-catenin, stem cell markers (CD133, CD166), Ki67 and pATMin 45 craniopharyngiomas and correlated it with clinicopathologic features.
Using the X-linked polymorphic androgen receptor gene as a tool for X-chromosome inactivating analysis, we found that a subset of craniopharyngiomas are monoclonal and therefore are probably due to acquired somatic genetic defects.
Targeted genotyping revealed BRAFp.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors).
In conclusion, mutation profiles of BRAF wild-type craniopharyngiomas and ameloblastomas share mutations of FGFR genes and have additional mutations with potential for targeted therapy.
In total, 14-50% of adult-onset craniopharyngioma are papillary; the majority with a mutation in exon 3 of BRAF and may respond to BRAF inhibitors and mitogen-activated protein kinase inhibitors.
As these targetable mutations warrant prospective research, the authors will be conducting a national National Cancer Institute-sponsored multicenter clinical trial to investigate BRAF/MEK inhibition in the treatment of craniopharyngioma.
A thorough analysis of the alterations of β-catenin/CTNNB1 and BRAF genes investigated in 1123 CP cases included in 27 studies, showed that, on average, CTNNB1 mutations were present in two-thirds of adamantinomatous CPs and BRAF mutations in 90% of papillary CPs.
Papillary craniopharyngiomas are defined by BRAF <sup>V600E</sup> mutations while β-catenin alterations characterize adamantinomatous craniopharyngiomas.
Here, we describe our treatment of a man age 39 years with multiply recurrent BRAFV600Ecraniopharyngioma using dabrafenib (150mg, orally twice daily) and trametinib (2mg, orally twice daily).
Although established approaches along with new surgical and radiotherapeutic approaches remain the main treatment modalities, recent evidence has provided insight into their molecular pathogenesis involving, other than chemotherapy, treatments with targeted agents as in gliomas and craniopharyngiomas bearing BRAF mutations.
Carbonic anhydrase IX, which is virtually absent in normal brain, is significantly upregulated in craniopharyngiomas and shows a significant association with cyst size.
In conclusion, the results suggest that P2X7R may promote IL-6, IL-8 and MCP-1 production and secretion and contribute to the invasion and adhesion of CPs to the surrounding tissue.
Moreover, the distributions of M2 macrophages, CD8+ T cells, and PD-L1 in papillary CPs were higher than those observed in adamantinomatous craniopharyngiomas (ACPs) (P = 0.0317, P = 0.0359, and P < 0.0001, respectively).
Our results revealed B7-H3 was highly expressed in CPs and targeting B7-H3 might therefore be an effective therapeutic strategy against craniopharyngioma.