Cancer is a complex disease characterized by the acquisition of mutations in oncogenes, tumor suppressors, and genes involved in the repair of DNA damage. Although Otto Warburg described that tumor cells use glycolysis to produce ATP instead of oxidizing glucose in the tricarboxylic acid cycle (TCA), it was not until recently that tumor metabolism has been studied in greater depth. The pioneering work of Warburg was the first step in understanding, not only the deregulation of glycolysis through an increase in the activity of different enzymes of the glycolytic pathway but also its post lactate dehydrogenase A.
Aberrant tumor metabolism is necessary to maintain the high proliferative rate, to escape the stress produced by the hypoxic shock, programmed cell death, the immune system, and the cells responsible for destroying tumor tissues. Recent findings show that there is an exquisite regulation of tumor metabolism exerted by oncogenes, as signaling pathways involved in cell growth and proliferation, such as the Pi3K / AKT pathway, actively regulates aerobic glycolysis. Transcriptional networks exert control in tumoral metabolic activities; thus, c-Myc activates the expression of LDH-A a metabolic enzyme that converts pyruvate (the final product of glycolysis) to lactate as well as glutamine synthetase. HIF-1a promote survival in hypoxic conditions by regulating genes important in glycolysis, redox homeostasis, etc. Sterol regulatory element-binding protein (SREBP) transcription factor is involved in the synthesis of fatty acids, activates different enzymes needed to convert acetyl-CoA into fatty acids.
Non-coding RNAs, such as lncRNAs and microRNAs (miRNAs), have been described as important regulators of the tumor microenvironment, involved in the development of cancer and the regulation of the different hallmarks of cancer. These non-coding molecules can regulate complex biological processes. They are modulators of adaptation to stressful situations such as hypoxia, oxidative stress, and nutrient deprivation.
Pharmacological strategies have been designed to inhibit aberrant tumor metabolism. However, the inhibition of enzymes involved in tumor metabolism often causes acute systemic toxicity, because the inhibitors also affect the enzymes of normal tissues. Therefore, the possibility of inhibiting metabolic pathways or specific enzymes will depend on whether the systemic blockade is tolerated. Examples that are already used in the oncology clinic include inhibitors of DNA synthesis such as antifolates (methotrexate, pemetrexed, and others). Although these drugs produce toxicity in normal proliferating tissues such as the intestinal epithelium and bone marrow, they are used in therapeutic schemes in different tumors. Although there are enzymes that are active exclusively in tumor cells, there are still no specific inhibitors in clinical practice. However, recent studies highlighting the potential of novel molecular targets for therapies represent an attractive approach in cancer.
We welcome original research and review articles that cover recent advances made to understand aberrant tumor metabolism and autophagy in cancer cells. Studies devoted to the identification and characterization of key regulators in tumor metabolism or autophagy (canonical genes, long non-coding RNAs, microRNAs, etc). Therapeutic approaches targeting tumor metabolism and autophagy are especially welcomed. This collection will cover, but is not limited to the following sub-topics:
- Metabolic pathways deregulated in cancer cells,
- Non-coding RNAs involved in the regulation of aberrant metabolism of cancer,
- Cellular and molecular mechanisms involved in the regulation of aberrant metabolism of cancer,
- Novel experimental approaches to understand how tumor cells reprogram their metabolism,
- Studies focused on the signaling pathways involved in the reprogramming of tumor metabolism,
- Tumor metabolism as a therapeutic target,
- Autophagy as an adaptive response to environmental stress,
- Autophagy metabolism as a therapeutic target.
Cancer is a complex disease characterized by the acquisition of mutations in oncogenes, tumor suppressors, and genes involved in the repair of DNA damage. Although Otto Warburg described that tumor cells use glycolysis to produce ATP instead of oxidizing glucose in the tricarboxylic acid cycle (TCA), it was not until recently that tumor metabolism has been studied in greater depth. The pioneering work of Warburg was the first step in understanding, not only the deregulation of glycolysis through an increase in the activity of different enzymes of the glycolytic pathway but also its post lactate dehydrogenase A.
Aberrant tumor metabolism is necessary to maintain the high proliferative rate, to escape the stress produced by the hypoxic shock, programmed cell death, the immune system, and the cells responsible for destroying tumor tissues. Recent findings show that there is an exquisite regulation of tumor metabolism exerted by oncogenes, as signaling pathways involved in cell growth and proliferation, such as the Pi3K / AKT pathway, actively regulates aerobic glycolysis. Transcriptional networks exert control in tumoral metabolic activities; thus, c-Myc activates the expression of LDH-A a metabolic enzyme that converts pyruvate (the final product of glycolysis) to lactate as well as glutamine synthetase. HIF-1a promote survival in hypoxic conditions by regulating genes important in glycolysis, redox homeostasis, etc. Sterol regulatory element-binding protein (SREBP) transcription factor is involved in the synthesis of fatty acids, activates different enzymes needed to convert acetyl-CoA into fatty acids.
Non-coding RNAs, such as lncRNAs and microRNAs (miRNAs), have been described as important regulators of the tumor microenvironment, involved in the development of cancer and the regulation of the different hallmarks of cancer. These non-coding molecules can regulate complex biological processes. They are modulators of adaptation to stressful situations such as hypoxia, oxidative stress, and nutrient deprivation.
Pharmacological strategies have been designed to inhibit aberrant tumor metabolism. However, the inhibition of enzymes involved in tumor metabolism often causes acute systemic toxicity, because the inhibitors also affect the enzymes of normal tissues. Therefore, the possibility of inhibiting metabolic pathways or specific enzymes will depend on whether the systemic blockade is tolerated. Examples that are already used in the oncology clinic include inhibitors of DNA synthesis such as antifolates (methotrexate, pemetrexed, and others). Although these drugs produce toxicity in normal proliferating tissues such as the intestinal epithelium and bone marrow, they are used in therapeutic schemes in different tumors. Although there are enzymes that are active exclusively in tumor cells, there are still no specific inhibitors in clinical practice. However, recent studies highlighting the potential of novel molecular targets for therapies represent an attractive approach in cancer.
We welcome original research and review articles that cover recent advances made to understand aberrant tumor metabolism and autophagy in cancer cells. Studies devoted to the identification and characterization of key regulators in tumor metabolism or autophagy (canonical genes, long non-coding RNAs, microRNAs, etc). Therapeutic approaches targeting tumor metabolism and autophagy are especially welcomed. This collection will cover, but is not limited to the following sub-topics:
- Metabolic pathways deregulated in cancer cells,
- Non-coding RNAs involved in the regulation of aberrant metabolism of cancer,
- Cellular and molecular mechanisms involved in the regulation of aberrant metabolism of cancer,
- Novel experimental approaches to understand how tumor cells reprogram their metabolism,
- Studies focused on the signaling pathways involved in the reprogramming of tumor metabolism,
- Tumor metabolism as a therapeutic target,
- Autophagy as an adaptive response to environmental stress,
- Autophagy metabolism as a therapeutic target.