Brain metastases (cancer) are the leading cause of morbidity and mortality in patients with tumors, and autopsies have shown that approximately 25% of patients who die from tumors have intracranial metastases. Clinical studies have shown that 2/3 of patients with intracranial metastases have symptoms during their survival time. 16-25% of breast cancer patients, 20-30% of lung cancer patients, and 40-60% of melanoma patients will develop brain metastases. The average survival time for patients with brain metastases is 4-6 months. Although the incidence of metastatic brain cancer is high, the mechanism of occurrence is not clear. With the increasing age of the population, the steady increase in the incidence of lung cancer, and the minimal change in tumor cure rates, there will be more problems associated with intracranial metastases. In addition, the use of more aggressive therapeutic approaches by some clinicians to treat tumors has prolonged the survival of tumor patients, while leading to a higher incidence of intracranial metastases. Currently, clinically, it is believed that the combination of surgery, radiotherapy and chemotherapy can prolong the survival of patients. Patients with primary tumors that can be eradicated and patients with single brain metastases without metastases from other sites who undergo radiotherapy after surgery have significantly longer survival and lower local recurrence rates, indicating that this combined approach is effective. The combined treatment method is suitable for some patients with brain metastases resistant to radiotherapy, or patients with large intracranial metastases, or patients whose condition deteriorates rapidly due to intracranial hemorrhage induced by metastases. 1. Transarterial metastasis The metastasis of lung, breast, gastrointestinal tract, kidney and other visceral tumors to intracranial area is mainly hematogenous. The tumor cells pass through the capillaries in the lung and then reach the brain by the carotid artery or vertebral artery to form the metastases. The metastases are mostly located in the subcortex, which are caused by the embolism of tumor cell emboli through the vascular rich gray matter into the less vascular white matter. 2. Metastasis via lymphatic system Tumor metastasis to intracranial area via lymphatic system is very rare. It is believed that the tumor cells of the primary tumor first metastasize to the nearby lymph nodes, and then spread to the brain surface by the lymphatic system through the neurointima of cerebral nerves or spinal nerves to the subarachnoid space. Therefore, it is actually a translymphatic-subarachnoid metastasis. 3. Trans-subarachnoid metastasis Very few spinal cord tumors metastasize intracranially through this route, which can be seen in astrocytoma, glioblastoma multiforme and intracranial implantation of ventricular meningioma. Occasionally, intraorbital tumors may also invade the skull along the optic nerve sheath and spread along the subarachnoid space. 4. Transvenous metastasis In the past, it was thought that some lung cancer or kidney cancer could also metastasize intracranially through the venous plexus of the vertebral vein system, but it was also suggested that from the distribution of metastases in the brain, there is no clear relationship with the venous system. II. Molecular biological basis of intracranial metastasis from primary tumor We know that brain metastasis cancer cells must first invade the blood-brain barrier, endothelial cells in the blood-brain barrier react to the invading malignant tumor cells, brain-derived pro-walking factors and CNS-derived invasion factors are secreted to break the blood-brain barrier, and CNS-derived survival and growth factors are secreted to make brain metastasis of malignant tumor cells occur successfully. Neurotrophins, such as NTs, play an important role in the invasion of metastatic cancer into the nervous system, especially the rejection of malignant tumor cells by brain tissue at the beginning of invasion, and NTs play a great role in ensuring the survival of the few invading malignant tumor cells. Neurotrophins produce basement membrane degrading enzymes through NT-dependent cells, allowing malignant tumor cells to break the blood-brain barrier. The expression of NT receptors on the membrane surface of invading malignant tumor cells is increased to enhance the invasiveness and survival of malignant tumor cells. For example, brain metastatic malignant melanoma cells secrete the same NTs (NGF, NT-3) as normal cells within the brain tissue. Paracrine production of Tf also plays a very important role in brain metastatic cancer, where invading malignant cells adapt to low concentrations of Tf by increasing the expression of receptors on their membrane surface. invading malignant cells also regulate the growth, invasiveness and survival of malignant cells within the host by producing autocrine and inhibitory factors. Synthetic paracrine factors and cytokines can affect neurotrophic factors secreted by normal brain tissue surrounding the tumor. For example, in normal brain tissue surrounding melanoma brain metastases, biopsy assays show significantly higher concentrations of NTs. Thus, the ability of a given malignancy to form metastatic carcinoma in the brain depends on the ability of tumor cells to respond to NTs, the ability of paracrine versus autocrine production of nerve growth factors, and other factors. Several recent studies have shown that the Stat3 network is involved in regulating the development and progression of brain metastatic carcinoma, and that EGF receptors activate the network of Stat3, leading to uncontrolled accretion, anti-angiogenesis, and invasive growth of metastatic tumors. The revelation of this phenomenon provides a theoretical basis for targeted therapy of brain metastatic tumors. The US FDA has recently approved a microarray technology for clinical application in breast metastatic cancer, detecting 70 gene chips in breast cancer to predict the likelihood of possible clinical metastasis of breast cancer. Gene expression profiling refers to the expression of all genes in a cell, i.e., the total sum of all mRNA expression profiles in a cell microarray, which is a large-scale parallel detection and analysis of mRNA or cDNA originating from tissues or cells using the advantages of gene microarrays such as high efficiency, sensitivity, high throughput, and parallelization. The probes are mixed and hybridized with the genes on the microarray, and then the microarray is scanned with a specific fluorescence wavelength to obtain the gene expression profiles of different tissues or cells, and then these differentially expressed genes are analyzed by bioinformatics research. Compared with traditional methods such as Northern blot or PCR, gene expression profiling microarrays have the advantages of high efficiency, sensitivity, high throughput and parallelization, and can study the genes associated with a certain phenotype or disease more comprehensively, making scientific research more purposeful and systematic. Using gene expression profiling microarrays, thousands of gene activation patterns in different tissues or cells can be obtained, making full use of the results of biological informatics It is possible to study the pathogenesis of diseases in a comprehensive and systematic way, breaking the pattern of “one gene for one disease” and emphasizing the networked mechanism of interconnections and interactions among genes, which jointly regulate the occurrence and development of diseases, and changing the way of thinking of research from reductionism to systematics. This chip provides new diagnostic and therapeutic ideas for the treatment of brain metastasis cancer, with the preventive treatment of primary tumors occurring in the brain. III. Treatment of brain metastases The treatment of intracranial metastases is more controversial, because there is no controlled and randomized clinical data, and it is difficult to draw objective conclusions about the evaluation of different treatment modalities such as radiotherapy, chemotherapy, and surgery. Almost all of the literature on the management of intracranial metastases is limited, mainly by the lack of comparability of several key factors, such as the stage of the systemic disease, the degree of neurological damage symptoms, the number and location of metastases, the sensitivity of the tumor cell type or the primary site to radiotherapy, and the combination of different treatment modalities. Nevertheless, surgical treatment has benefits for most patients, including improved quality of survival and longer survival time. In recent years, with the improvement of early diagnosis and the progress of comprehensive treatment for malignant tumors, there is a tendency to adopt an aggressive treatment plan for intracranial metastases. The effective treatments for brain metastases are the same as those for primary brain tumors, including corticosteroids, radiation therapy, surgery, and chemotherapy. Picking the most appropriate treatment for brain metastases is more time-consuming than for primary brain tumors because it requires a complete assessment of the patient’s systemic condition, not just the local lesion. Treatment of intracranial metastases takes into account: the size, location, and histologic nature of the tumor, the patient’s age, neurologic status, and general condition, as well as the potential for peripheral spread of the intracranial metastases, the extent of the tumor, the potential responsiveness of the tumor to treatment, and the potential damage to other systemic organs from initial treatment. Factors affecting survival after surgery in patients with brain metastases include preoperative neurological status, the time interval between the primary tumor and the detection of intracranial metastases, and most importantly, the extent of the primary disease, as the primary cause of death in this group of patients lies in the extent of the extra-neurological primary tumor. Preoperative evaluation should include: radiological examination of the chest, radionuclide scans of the bone and liver and spleen. CT and MRI are also needed for further confirmation of suspected metastases or residual primary tumors. Particularly in patients with metastases indicated for surgery, rigorous preoperative imaging and laboratory testing of the patient is extremely important in determining the surgical procedure. Double-dose CT imaging or MRI scans may reveal occult intracranial metastatic lesions. Evaluation of cardiopulmonary function is necessary for patients undergoing major pneumonectomy or receiving chemotherapy with pneumotoxic or cardiotoxic chemotherapeutic agents. In all oncology patients especially those who have undergone or are undergoing chemotherapy, their clotting time should be monitored. While most chemotherapeutic agents are good predictors of declining bone marrow function, in patients undergoing elective surgery, chemotherapy should be prompt and accompanied by daily monitoring of routine blood changes to ensure that surgery is performed when platelets and white blood cells are normal. Targeted therapy is expected to be one of the new strategies for the treatment of brain metastases. The targets of treatment include EGFR and its tyrosine kinase endogenous signaling pathway, matrix metalloproteinases, cell cycle pathway and apoptotic pathway. Targeted therapeutic agents that have entered the clinical research field of brain metastases are mainly EGFR-TKI, such as gefitinib and lapatinib, etc. Recent studies have confirmed that molecular targeted drugs such as gefitinib and lapatinib have shown better efficacy in brain metastases.