Trim7 expression regulates the Wnt/b-catenin signaling pathway involved in the mechanism of drug resistance in prolactin adenoma DAs

The annual incidence of pituitary adenomas in the population is as high as 7.5-15/100,000 people, and pituitary prolactinoma (prolactinoma) is the most common pituitary adenoma with endocrine function, accounting for about 45-70% of all pituitary adenomas. With the improvement of people's health awareness and the advancement of diagnostic technology, imaging equipment, and surgical level, the number of actual patients diagnosed in clinic is significantly higher than the above The actual number of clinically diagnosed patients is significantly higher than the above data. Prolactin adenomas are often characterized by infertility, amenorrhea, and breast milk overflow in women due to hyperprolactinemia, decreased libido and sexual function and infertility in men, as well as symptoms of pressure including headache, vision loss, and visual field damage. These symptoms seriously affect patients' quality of life, and the number of deaths and disabilities associated with them has been increasing in recent years, placing a heavy burden on society and families.Currently, the main treatment for pituitary prolactin adenomas is drug therapy, and dopamine agonist (DAs) is the first choice for treatment, and the DAs used as the first-line drugs in clinical practice are bromocriptine and cabergoline, etc. The DAs can be used as a first-line drug to treat prolactin adenomas by interacting with the surface of the cell surface. DAs are able to inhibit PRL production and secretion and mediate tumor volume contraction by specifically binding to dopamine receptors on the cell surface of prolactin adenomas. However, there are still about 10-25% of patients who are insensitive to DAs, i.e., Dopamie agonist resistant prolactinomas (DARPs), in the current clinical treatment. Currently, there is no strict international definition of DARPs, but from the endocrine point of view, the main point of view is failure to normalize serum PRL levels. From an endocrine point of view, the definition of DARPs is failure to normalize serum PRL levels. In terms of tumor size reduction, it is generally defined as a failure to reduce tumor size by at least 50% with the maximum conventional dose of drugs (bromocriptine 15mg/d or cabergoline 3mg/wk) for at least 3 consecutive months. Currently about 17% of patients treated with cabergoline fail to reduce PRL levels to the normal range.Currently, in clinical practice, the main choice of non-pharmacologic treatment for patients with DARPs is surgery and radiation therapy. However, the results of surgical treatment in patients with DARPs are poor.Hamilton DK et al. reported that only 36% of 61 patients with DARPs after surgical treatment had normalized PRL levels after surgery [9]. Epidemiologic studies have shown that DARPs are more likely to invade the cavernous sinus, which is invaded by about 71% of DARPs, compared with only 10% of sensitive prolactinomas. Radiation therapy, such as Gamma Knife therapy, may be used for DARPs that are surgical remnants. Unfortunately, however, prolactinomas are the least sensitive functional pituitary adenomas to radiotherapy, with a 4-year PRL hormone remission rate of only 18%, and a remission rate of only 16% after gamma knife treatment. Therefore, surgical treatment and radiation therapy for DARPs remain ineffective and their clinical management is tricky.Therefore, as a supplement to the existing therapeutic regimens for DARPs, it is necessary to develop new therapeutic agents based on the mechanism of occurrence of DARPs. Decitabine (DAC) is a DNA methyltransferase (DNMT) inhibitor that induces DNA demethylation, enabling the restoration of key genes that are essential for cellular differentiation and proliferation, thereby exerting antitumor effects.