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Potentiation of anti-cancer treatment by modulators of energy metabolism
1Dept of Oncology-Pathology, CCK R8:03, Karolinska Institute, S-171 76 Stockholm, Sweden. mimmi.shoshan@ki.se
Abstract:
Oncogene-driven proliferative signaling in tumor cells requires comprehensive upregulation of cellular energy metabolism and macromolecule syntheses. These alterations are now known to include not only upregulated glycolysis, but also increased fatty acid metabolism, glutaminolysis, deregulated mitochondrial function and more. Many prospective targets for tumor-specific pharmacological modulation of metabolism have therefore been identified. While the prospective drugs do not necessarily show very high antitumor activity by themselves, they may by depriving tumor cells of energy and building blocks for repair and proliferation come to be of major clinical use as potentiators of standard chemotherapeutic drugs and/or radiation. To this end, not only inhibitors of specific enzyme functions are being investigated, but also drugs affecting the complex signaling networks that regulate organismal and cellular energy status. This review provides examples of how modulators of energy metabolism (MEMs) targetting different aspects of tumor cell metabolism have been found to potentiate cancer treatment in vitro and in vivo.
Insights
Cancer cells reprogram metabolism for growth. Modulators of energy metabolism (MEMs) can enhance chemotherapy and radiation by targeting tumor cell energy pathways, improving treatment outcomes.
Area of Science:
- Oncology
- Cancer Metabolism
- Pharmacology
Background:
- Oncogene-driven cancer cells exhibit increased energy metabolism and macromolecule synthesis.
- Metabolic alterations include upregulated glycolysis, fatty acid metabolism, glutaminolysis, and deregulated mitochondrial function.
- These metabolic changes present numerous targets for pharmacological intervention.
Purpose of the Study:
- To review modulators of energy metabolism (MEMs) that target various aspects of tumor cell metabolism.
- To provide examples of how MEMs can potentiate cancer treatment in vitro and in vivo.
- To highlight the potential clinical utility of MEMs as adjuncts to standard cancer therapies.
Main Methods:
- Review of scientific literature on cancer metabolism and therapeutic interventions.
- Analysis of studies investigating the effects of MEMs on tumor cell metabolism.
- Evaluation of preclinical (in vitro and in vivo) data on MEMs in combination with chemotherapy and radiation.
Main Results:
- Numerous targets for modulating tumor cell metabolism have been identified.
- MEMs can deprive cancer cells of essential energy and building blocks.
- Preclinical studies demonstrate that MEMs can potentiate the efficacy of standard cancer treatments.
Conclusions:
- Modulators of energy metabolism show promise in enhancing cancer treatment.
- Targeting tumor cell metabolism offers a strategy to overcome treatment resistance.
- MEMs may become clinically valuable as potentiators of chemotherapy and radiation therapy.
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