Targeting the Warburg Effect in Hematological Malignancies: from PET to Therapy
Posted: Sat Oct 24, 2015 5:47 am
Targeting the Warburg Effect in Hematological Malignancies: from PET to Therapy
Purpose of Review
To highlight key studies providing rationale for and utility in targeting glycolysis for the treatment of hematological malignancies.
Recent Findings
Several therapeutic strategies are capitalizing on the diagnostic utility of FDG-PET that relies on increased glycolysis and glucose utilization in tumor cells. While aerobic glycolysis was initially proposed by Warburg to be due to mitochondrial impairment, recent studies have shown a preferential switch to glycolysis in tumor cells with functional mitochondria. Increased glucose consumption can be advantageous for a tumor cell through stimulation of cellular biosynthetic, energetic, and pro-survival pathways. We now have a greater appreciation for the utilization of glucose in specific metabolic pathways that in some aspects can be complemented with other nutrients such as glutamine. Targeting glucose consumption for the treatment of hematological malignancies seems to be a promising field that will require characterization of tumor cell specific targets to inhibit glucose uptake and/or glycolysis. It is imperative to further our understanding of the tumor cell metabolome to target cellular bioenergetics in the treatment of cancer.
Summary
Targeting the glycolytic pathway for the treatment of hematological malignancies has sufficient rationale given the utility of FDG-PET in diagnostic imaging. Further research is required in developing tumor cell specific therapeutics.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879327/
The role of FDG-PET scans in patients with lymphoma
http://m.bloodjournal.org/content/110/10/3507.full
Purpose of Review
To highlight key studies providing rationale for and utility in targeting glycolysis for the treatment of hematological malignancies.
Recent Findings
Several therapeutic strategies are capitalizing on the diagnostic utility of FDG-PET that relies on increased glycolysis and glucose utilization in tumor cells. While aerobic glycolysis was initially proposed by Warburg to be due to mitochondrial impairment, recent studies have shown a preferential switch to glycolysis in tumor cells with functional mitochondria. Increased glucose consumption can be advantageous for a tumor cell through stimulation of cellular biosynthetic, energetic, and pro-survival pathways. We now have a greater appreciation for the utilization of glucose in specific metabolic pathways that in some aspects can be complemented with other nutrients such as glutamine. Targeting glucose consumption for the treatment of hematological malignancies seems to be a promising field that will require characterization of tumor cell specific targets to inhibit glucose uptake and/or glycolysis. It is imperative to further our understanding of the tumor cell metabolome to target cellular bioenergetics in the treatment of cancer.
Summary
Targeting the glycolytic pathway for the treatment of hematological malignancies has sufficient rationale given the utility of FDG-PET in diagnostic imaging. Further research is required in developing tumor cell specific therapeutics.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879327/
The role of FDG-PET scans in patients with lymphoma
http://m.bloodjournal.org/content/110/10/3507.full