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dc.contributor.authorRaczka, Aleksandra Maria
dc.contributor.authorReynolds, Paul Andrew
dc.identifier.citationRaczka , A M & Reynolds , P A 2019 , ' Glutaminase inhibition in renal cell carcinoma therapy ' , Cancer Drug Resistance , vol. 2 .
dc.descriptionThis work was supported by the Melville Trust for Care and Cure of Cancer.en
dc.description.abstractReceptor tyrosine kinase inhibitors have been a standard first-line therapy for renal cell carcinoma (RCC) for over a decade. Although they stabilize the disease, they are unable to remove all tumor cells, leading to relapse. Moreover, both intrinsic and acquired resistance to therapy are a significant health burden. In order to overcome resistance, several combination therapies have been recently approved by the FDA. Another approach takes advantage of altered metabolism in tumor cells, which switch to alternative metabolic pathways to sustain their rapid growth and proliferation. CB-839 is a small molecule inhibitor of kidney type glutaminase (GLS). GLS is often upregulated in glutamine addicted cancers, enhancing glutamine metabolism for the production of energy and the biosynthesis of various cellular building blocks. CB-839 is currently in clinical trials for several tumors, including clear cell (cc)RCC, both as monotherapy and in combination with the approved therapeutic agents everolimus, cabozantinib and nivolumab. Early results of Phase 1/2 clinical trials look promising, especially for CB-839 plus cabozantinib, and all combinations seem to be well tolerated. However, cancer cells can activate compensatory pathways to overcome glutaminolysis inhibition. Therefore, genetic and metabolomic studies are crucial for the successful implementation of CB-839 alone or in combination in subgroups of ccRCC patients.
dc.relation.ispartofCancer Drug Resistanceen
dc.subjectGlutamine addictionen
dc.subjectRenal cell carcinoma (RCC)en
dc.subjectCombination therapyen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleGlutaminase inhibition in renal cell carcinoma therapyen
dc.typeJournal itemen
dc.contributor.sponsorThe Melville Trust for the Care & Cureen
dc.contributor.institutionUniversity of St Andrews. Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews. Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Centre for Biophotonicsen
dc.description.statusPeer revieweden

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