Metabolic Modulation of Glioblastoma with Dichloroacetate

By E. Michelakis, G. Sutendra, P. Dromparis, L. Webster, A. Haromy, E. Niven, C. Maguire, Terri-Lynn Gammer, John R. Mackey, D. Fulton and 3 more. Science Translational Medicine, 2010

753 citations recorded by the source corpus.

Subfields: Cancer Research, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/48caf59f93a6d7e89dfe4c537896e40a8893da02

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. C. V. Dang
2. G. Semenza
3. Jason W. Locasale
4. Ming Tan
5. M. V. Vander Heiden
6. Ping Gao
7. Huafeng Zhang
8. Qingsong Cai

In Genetics

1. C. V. Dang
2. G. Semenza
3. J. Rathmell
4. Nancie J. MacIver
5. Jason W. Locasale
6. M. V. Vander Heiden
7. Christopher B. Newgard
8. Navdeep S. Chandel

In Molecular Biology

1. C. V. Dang
2. Jason W. Locasale
3. G. Semenza
4. M. V. Vander Heiden
5. Ming Tan
6. Ping Gao
7. Huafeng Zhang
8. Jianrong Lu

Citations in the corpus

• HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. (2013, positive): “In a clinical study of three patients with glioblastoma multiforme, comparison of tumor tissue before and after DCA treatment revealed increased PDH activity, decreased proliferation, increased apoptosis, decreased HIF-1 α levels, and decreased angiogenesis after therapy (105).”
• Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. (2015, positive): “Indeed, DCA can suppress aerobic glycolysis of cancer cells and stimulate ROS production that can lead to cancer cell senescence (15, 18).”
• The Warburg effect in tumor progression: Mitochondrial oxidative metabolism as an anti-metastasis mechanism (2014, background): “This metabolic normalization increases mitochondrial respiration and ROS generation, and induces apoptosis in certain cancer cells even under attached conditions [89] [90].”
• Mechanisms of disease: pulmonary arterial hypertension (2011, background): “[169] [170] [171] Clinical studies in glioblastoma multiforme have begun, 172 and a clinical trial of dichloroacetate in PAH is also underway.”
• Targeting cancer metabolism: a therapeutic window opens (2011, background): “, and has been shown to alter mitochondria in patients with glioblastom”
• Otto Warburg's contributions to current concepts of cancer metabolism (2011, background): “Hence, targeting metabolism for cancer therapy holds promise for new classes of anti-neoplastic drug”
• Metabolic reprogramming and epigenetic modifications on the path to cancer (2021, background): “The reactivation of PDC by DCA therapy rectifies the balance between the demand and supply of oxygen, leading to cancer cell death (Michelakis et al., 2010; Dunbar et al., 2014; Chu et al., 2015; Zhang et al., 2015).”
• Understanding the intersections between metabolism and cancer biology (2017, neutral): “The PDHK inhibitor dichloroacetate (DCA) elicits metabolic effects in human tumors (Michelakis et al., 2010), but minimal efficacy data has been reported.”