Analysis of Therapeutic Targets in Cancer Stem Cells Using Integrated Proteomics

Abstract

Recent cancer research has identified the existence of cancer stem cells (CSCs), which have been highlighted as the root cause of chemotherapeutic resistance and recurrence in cancer. Targeting cancer stem cells and their microenvironment (niche) holds great potential for developing innovative therapeutic strategies. However, there are still challenges due to the lack of easily accessible experimental model cells and insufficient information on CSC proteomics and genomics, as well as specific CSC markers. As a consequence, detailed molecular and functional information on cancer stem cells remains largely missing, making the development of targeted therapies extremely difficult.

To address these challenges, we have successfully established CSCs and their differentiation induction models from various patient tumor tissues/cells. By integrating comparative expression analyses of proteome and mRNA data from these models, we have made it possible to obtain detailed molecular information on cancer stem cells.

This article focuses on malignant glioma stem cells (GSC) as the primary analysis model. It introduces methodologies to understand the molecular network dynamics involved in the maintenance and differentiation-switching of glioma stem cells based on these quantitative molecular data in a comprehensive manner. Additionally, key factors mediating the mutual induction between CSC and cancer cells, as well as specific signals that have been successfully identified in a comprehensive manner as therapeutic targets through these analyses are highlighted.