Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Altered cellular metabolism is a hallmark of cancer. Cancer cells express isoforms of metabolic enzymes that may constitute therapeutic targets. Glutaminase controls glutamine metabolism and their expression correlate with malignancy of tumours. The two types of glutaminase isoenzymes, GLS and GLS2, differ in their expression patterns and functional roles: GLS has oncogenic properties and GLS2 has been described as a tumour suppressor factor. Selective genomic and epigenomic intervention over glutaminase affects the metabolic reprogramming of cancer. This review highlights the molecular metabolic vulnerabilities in various types of cancer, to be used for biomarker development, drug design, and in personalized oncology.
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PMID:Glutaminase isoenzymes in the metabolic therapy of cancer. 3005 97

Increased glutamine metabolism (glutaminolysis) is a hallmark of cancer and is recognised as a key metabolic change in cancer cells. Breast cancer is a heterogeneous disease with different morphological and molecular subtypes and responses to therapy, and breast cancer cells are known to rewire glutamine metabolism to support survival and proliferation. Glutaminase isoenzymes (GLS and GLS2) are key enzymes for glutamine metabolism. Interestingly, GLS and GLS2 have contrasting functions in tumorigenesis. In this review, we explore the role of glutaminase in cancer, primarily focusing on breast cancer, address the role played by oncogenes and tumour suppressor genes in regulating glutaminase, and discuss current therapeutic approaches to targeting glutaminase.
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PMID:The role of glutaminase in cancer. 3159 4

Targeted therapies against cancer have improved both survival and quality of life of patients. However, metabolic rewiring evokes cellular mechanisms that reduce therapeutic mightiness. Resistant cells generate more glutathione, elicit nuclear factor erythroid 2-related factor 2 (NRF2) activation, and overexpress many anti-oxidative genes such as superoxide dismutase, catalase, glutathione peroxidase, and thioredoxin reductase, providing stronger antioxidant capacity to survive in a more oxidative environment due to the sharp rise in oxidative metabolism and reactive oxygen species generation. These changes dramatically alter tumour microenvironment and cellular metabolism itself. A rational design of therapeutic combination strategies is needed to flatten cellular homeostasis and accomplish a drop in cancer development. Context-dependent glutaminase isoenzymes show oncogenic and tumour suppressor properties, being mainly associated to MYC and p53, respectively. Glutaminases catalyze glutaminolysis in mitochondria, regulating oxidative phosphorylation, redox status and cell metabolism for tumour growth. In addition, the substrate and product of glutaminase reaction, glutamine and glutamate, respectively, can work as signalling molecules moderating redox and bioenergetic pathways in cancer. Novel synergistic approaches combining glutaminase inhibition and redox-dependent modulation are described in this review. Pharmacological or genetic glutaminase regulation along with oxidative chemotherapy can help to improve the design of combination strategies that escalate the rate of therapeutic success in cancer patients.
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PMID:Glutaminases regulate glutathione and oxidative stress in cancer. 3268 Nov 90