Craniopharyngioma

A craniopharyngioma is a slow-growing non-cancerous brain tumor in the pituitary and hypothalamus. Craniopharyngioma is a benign tumor that does not spread like cancer, but it has the potential to grow and surrounds very important nerves and blood vessels at the base of the brain and near the pituitary and hypothalamus. The tumor can eventually grow enough to compress the normal pituitary gland, resulting in the loss of normal hormones important for normal life and reproduction.

Figure 1. Features of craniopharyngioma. (Müller, H. L., et al., 2019)

Although craniopharyngioma has a low incidence and low pathological classification (WHO grade I), its location in the saddle area, adjacent to important structures such as the pituitary stalk and hypothalamus, makes it more difficult to operate, with more perioperative complications and a poorer patient prognosis. At a time of rapid advances in molecular biology, Alfa Cytology offers the possibility for customers to further explore the molecular mechanisms of craniopharyngioma and use them to develop targeted drugs, which will undoubtedly be one of the directions for the treatment of craniopharyngioma.

• Genetic mutations

Mutations in the CTNNB1 gene block the phosphorylation and degradation of β-chain proteins, leading to the deposition of β-chain proteins in the nucleoplasm and further activation of the WNT/β-catenin signaling pathway, leading to tumorigenesis.

The majority of patients with enamel epidermoid craniopharyngioma also have mutations in the β-catenin gene, which activate the WNT pathway and cause alterations in the MEK/ERK pathway, resulting in greater proliferation and invasion of tumor cells, leading to the development of enamel epidermoid craniopharyngioma. Although drugs targeting the β-catenin gene and its downstream MAPK pathway are not yet in clinical trials, they have shown significant efficacy in vitro studies and are expected to be new targets for clinical treatment.

• Signal transduction pathways

Specific MEK inhibitors reduce the number of enucleated epidermal craniopharyngioma cells, reduce the proliferation capacity of tumor cells and promote apoptosis by inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway.

BRAF protein, an upstream regulator of the MAPK signaling pathway, regulates a variety of physiological processes and is upregulated in tumor cells. Normal pituitary SOX2 stem cells may activate the MAPK pathway through mutations in the BRAF gene and transform into papillary craniopharyngioma cells, leading to tumorigenesis.

Specific genetic mutations in craniopharyngioma expand the selectivity of treatment and provide direction for novel molecularly targeted drugs for individualized treatment. Alfa Cytology can help customers to analyze the molecular profile of the enzymatic epidermal craniopharyngioma pathway to reveal potentially therapeutically relevant signaling pathways and thus advance the targeting of small molecule inhibitors, including SHH signaling pathway inhibitors, BRAF inhibitors, and MEK inhibitors. We can also help you identify the upregulation of several markers that may represent potential therapeutic targets, including IL-6, PD1/PD-L1, IDO-1, and more. Please feel free to contact us to submit your requirements.