Targeted molecular ablation of cancer stem cells for curing gastrointestinal cancers

ABSTRACT

Introduction: Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis.

Areas covered: A novel approach to ablate CSCs in GI cancers, including esophageal, gastric, and colon cancers, is introduced along with explored underlying molecular mechanisms.

Expert commentary: Though CSC ablation is still in the empirical stages and not in clinical practice, several strategies for ablating CSCs in GI cancers had been published, proton-pump inhibitors (PPIs) that regulate the membrane-bound ABC transporters, which underlie drug resistance; chloroquine (CQ) that inhibits autophagy, which is responsible for tumor survival; Hedgehog/Wnt/Notch inhibitors that influence the underlying stem-cell growth, and some natural products including Korean red ginseng, cancer-preventive kimchi, Artemisia extract, EGCG from green tea, and walnut extracts.

KEYWORDS:

• Cancer stem cells
• GI cancers
• proton pump inhibitors
• sonic hedgehog inhibitor
• chloroquine
• kimchi

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This research was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through High Value-added Food Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (116015-03-1-CG000).