Exploring novel personalized treatment options focusing on cancer stem cells

It is well known that cancer stem cells (CSCs) play a pivotal role in tumor metastasis, recurrence, heterogeneity, and resistance to chemotherapy and radiotherapy with poor prognosis in various cancers. Therefore, CSCs are promising targets for cancer treatment, which when effectively executed could ultimately improve patient prognosis. The work described in this thesis examined roles of some CSCs-related pathways including MTA3, ChRNA7, A-PaschiRNA, and mTOR in both cancer development, and maintenance and acquirement of cancer stemness, as defined by tumor cell dissemination and metastatic potential, as well as stem cell properties in cancer models. This thesis also revealed several underlying regulatory mechanisms of these pathways. Targeting these CSCs-related pathways using drugs that are currently existing or that will be developed could serve as a method to eliminate CSCs. Moreover, we also explored the potential of CSCs to predict patient response using CSCs-originating 3D cultured patient-derived organoids (PDOs), because accumulating evidence has showed CSCs can result in resistance to treatment. The preliminary results of this part suggest a potential of esophageal adenocarcinoma (EAC) patient’s tumor specific-derived organoids (ec-PDOs) to predict patient-specific responses to neoadjuvant chemoradiotherapy. Further characterization and optimization of ec-PDOs culture systems may offer huge potential as a model for predicting patient-specific responses to clinical neoadjuvant chemoradiotherapy for EAC patients. In conclusion, this thesis focused on CSCs to explore novel personalized treatment options