Journal of Digestive Cancer Research

Korean Society of Gastrointestinal Cancer Research (대한소화기암연구학회)
권호 표지

Chemoquiescence with Molecular Targeted Ablation of Cancer Stem Cells in Gastrointestinal Cancers

  • Jong-Min Park (CHA Cancer Prevention Research Center, CHA University) ;
  • Young-Min Han (CHA Cancer Prevention Research Center, CHA University) ;
  • Migyeong Jeong (CHA Cancer Prevention Research Center, CHA University) ;
  • Eun Jin Go (CHA Cancer Prevention Research Center, CHA University) ;
  • Napapan Kangwan (Department of Biochemistry, University of Phayao) ;
  • Woo Sung Kim (CHA Cancer Prevention Research Center, CHA University) ;
  • Ki Baik Hahm (CHA Cancer Prevention Research Center, CHA University)
  • Received : 2016.04.05
  • Accepted : 2016.06.16
  • Published : 2016.06.30
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Abstract

The abundance of multi-drug resistance ATPase binding cassette and deranged self-renewal pathways shown in cancer stem cells (CSCs) played a crucial role in tumorigenesis, tumor resistance, tumor recurrence, and tumor metastasis. Therefore, elucidation of CSCs biology can improve diagnosis, enable targeted treatment, and guide the follow up of GI cancer patients. In order to achieve chemoquiescence, seizing cancer through complete ablation of CSCs, CSCs are rational targets for the design of interventions that will enhance responsiveness to traditional therapeutic strategies and contribute in the prevention of local recurrence as well as metastasis. However, current cancer treatment strategies fail to either detect or differentiate the CSCs from their non-tumorigenic progenies mostly due to the absence of specific biomarkers and potent agents to kill CSCs. Recent advances in knowledge of CSCs enable to produce several candidates to ablate CSCs in gastrointestinal (GI) cancers, especially cancers originated from inflammation-driven mutagenesis such as Barrett's esophagus (BE), Helicobacter pylori-associated gastric cancer, and colitis-associated cancer (CAC). Our research teams elucidated through revisiting old drugs that proton pump inhibitor (PPI) and potassium competitive acid blocker (p-CAB) beyond authentic acid suppression, chloroquine for autophage inhibition, sonic hedgehog (SHH) inhibitors, and Wnt/β-catenin/NOTCH inhibitor can ablate CSCs specifically and efficiently. Furthermore, nanoformulations of these molecules could provide an additional advantage for more selective targeting of the pathways existing in CSCs just like current molecular targeted therapeutics and sustained action, while normal stem cells intact. In this review article, the novel approach specifically to ablate CSCs existing in GI cancers will be introduced with the introduction of explored mode of action.

Keywords

Acknowledgement

Supported by This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2014 R1A1A2058732)

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