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Metabolic Modification in Gastrointestinal Cancer Stem Cells: Characteristics and Therapeutic Approaches
Angela Maria Di Francesco1, Amelia Toesca2, Carlo Cenciarelli3
1Laboratory of Pharmacology, Division of Paediatric Oncology, Gemelli Hospital, Rome, Italy.
Abstract:
Currently, there is much interest in the characterization of metabolic profiling of cancer stem cells (CSCs), a small subset of tumor cells with self-renewal capacity. Indeed, ever-growing evidence indicate that metabolism and stemness are highly intertwined processes in tumor tissue. In this review, we analyze the potential metabolic targeting strategies for eradicating CSCs that could help to develop a more effective therapeutic approach for gastrointestinal cancers. Indeed, the successful elimination of a tumor requires an anticancer therapy that affects both cancer cells and CSCs. The observation that gastrointestinal CSCs possess higher inducible nitric oxide sinthase (iNOS) expression, lower reactive oxygen species (ROS) production, and a different metabolism respect to no-CSCs tumor cells has paved the way to develop drugs targeting CSC specific signaling. In particular, several studies have highlighted that metformin, aldehyde dehydrogenase 1, and iNOS inhibitors selectively suppressed CSC growth and that combinatorial therapy of them with standard chemotherapeutic drugs had a synergistic effect resulting in reduced tumor burden and delayed tumor recurrence. Thus, the possibility of combining specific CSC metabolism inhibitors with existing therapeutic approaches could have profound anticancer effects, changing the conventional treatment approaches to gastrointestinal cancers. J. Cell. Physiol. 231: 2081-2087, 2016. © 2016 Wiley Periodicals, Inc.
Insights
Targeting cancer stem cells (CSCs) metabolism offers a new strategy for gastrointestinal cancer treatment. Inhibiting CSC-specific pathways with drugs like metformin can synergize with chemotherapy, reducing tumor burden and recurrence.
Area of Science:
- Oncology
- Cancer Metabolism
- Gastrointestinal Cancers
Background:
- Cancer stem cells (CSCs) are crucial for tumor growth and recurrence.
- Metabolism and stemness are closely linked in tumor biology.
- Gastrointestinal CSCs exhibit distinct metabolic profiles compared to non-CSCs.
Purpose of the Study:
- To review metabolic targeting strategies for eradicating CSCs in gastrointestinal cancers.
- To explore the potential of combining CSC-specific metabolism inhibitors with standard therapies.
Main Methods:
- Literature review of studies on CSC metabolism and therapeutic strategies.
- Analysis of metabolic differences between CSCs and non-CSCs, including iNOS and ROS levels.
- Evaluation of drug efficacy, including metformin, aldehyde dehydrogenase 1, and iNOS inhibitors, alone and in combination therapy.
Main Results:
- Gastrointestinal CSCs show higher inducible nitric oxide synthase (iNOS) expression and lower reactive oxygen species (ROS) production.
- Metformin, aldehyde dehydrogenase 1, and iNOS inhibitors selectively inhibit CSC growth.
- Combination therapy with these inhibitors and standard chemotherapy demonstrates synergistic effects, reducing tumor burden and delaying recurrence.
Conclusions:
- Targeting CSC metabolism is a promising strategy for improving gastrointestinal cancer treatment.
- Combinatorial approaches involving CSC metabolism inhibitors and conventional chemotherapy can enhance therapeutic outcomes.
- This approach holds potential to revolutionize conventional treatment strategies for gastrointestinal cancers.
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