Research Of Precision Medicine Strategy Based On Cancer Stem Cells

Brain tumors are the most common neurological diseases,which occur in the central nervous system(CNS).In recent years,the incidence of brain tumors has been on the rise.Currently,the common treatment method for brain tumors is surgical resection combined with radiation therapy,but the majority of malignant brain tumors,especially gliomas showed diffuse infiltration of white matter tracts,as a result,it is almost impossible to achieve complete resection through surgery.Cancer stem cells are a group of cells present in tumors with characteristics of stem cells.It has been demonstrated in many types of tumors that the existence of cancer stem cells is one of the important causes of tumor recurrence and insensitivity to radiotherapy and chemotherapy.Therefore,the therapeutic strategy for cancer stem cells becomes the new focus of cancer research.The exploration of the molecular mechanisms of cancer stem cells has also become the key to understanding tumors.Fortunately,the development of high-throughput sequencing has provided strong technical support.In view of this situation,we obtained glioma stem cell lines in vitro and then performed genome sequencing of patients' tumor tissue and cancer stem cells to obtain their gene mutation information.At the same time,we performed drug screening in vitro to find drugs targeting glioma stem cells,which provided new directions for clinical treatment.Chapter 1: At the beginning,the characteristics of the central nervous system tumors and the current clinical treatment methods are systematically summarized,followed with research status of cancer stem cells,including their characteristics and methods of cultivation and identification.Next is description of the development and application of high-throughput sequencing technologies and its important role in the current cancer research.Finally,the concept of precision medicine is introduced,which provides new solutions for tumor research and therapy.Chapter 2: This section is about isolation,culture and identification of primary cancer stem cells.We obtained fresh tumor tissue samples from hospitals,and then isolated glioma stem cells.After that,we identified the cultured cells in vitro and in vivo.The results show that our culture system can successfully establish glioma stem cell lines.Chapter 3: High-throughput sequencing technology is an indispensable technique for tumor research.We used various sequencing methods such as whole genome sequencing,whole exon sequencing,and RNA-seq to analyze the gene mutation information of patients.Here we report a case of primary meningioma with simultaneous lung metastases.We analyzed and discussed its whole exon sequencing result and found that the meningioma may be driven by the inactivation of the NF2 gene and subsequent accumulation and activation of the YAP1 protein.Chapter 4: To better integrate with clinical treatment,we performed drug screening on glioma stem cells in vitro and found that the proteasome inhibitor Bortezomib can specifically kill G98,and its functional analogue DSF-Cu can also have a very significant growth inhibition effect on G98 in low concentration.In summary,we have established a complete and effective method for isolation and culture of glioma stem cells.Then we sequenced patients' tumor tissue and cancer stem cells by high-throughput sequencing to obtain information of gene mutations.Furthermore,we also conducted drug screening on glioma stem cells in vitro and analyzed both genetic information and drug information,which provides more possibilities for clinical treatment.