2. Academic Validation
  3. Inhibition of monocarboxylate transporter-1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport

Inhibition of monocarboxylate transporter-1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport

  • Mol Cancer Ther. 2014 Dec;13(12):2805-16. doi: 10.1158/1535-7163.MCT-13-1091.
Becky M Bola 1,  Amy L Chadwick 2,  Filippos Michopoulos 3,  Kathryn G Blount 4,  Brian A Telfer 4,  Kaye J Williams 4,  Paul D Smith 3,  Susan E Critchlow 3,  Ian J Stratford 5
Affiliations

Affiliations

  • 1 Manchester Pharmacy School, Manchester Cancer Research Centre, University of Manchester, Manchester, United Kingdom. Clinical and Experimental Pharmacology, CR-UK Manchester Institute, Manchester, United Kingdom.
  • 2 Manchester Pharmacy School, Manchester Cancer Research Centre, University of Manchester, Manchester, United Kingdom. Breakthrough Breast Cancer, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
  • 3 Oncology iMED, AstraZeneca, Mereside, Cheshire, United Kingdom.
  • 4 Manchester Pharmacy School, Manchester Cancer Research Centre, University of Manchester, Manchester, United Kingdom.
  • 5 Manchester Pharmacy School, Manchester Cancer Research Centre, University of Manchester, Manchester, United Kingdom. ian.stratford@manchester.ac.uk.
PMID: 25281618 DOI: 10.1158/1535-7163.MCT-13-1091
Abstract

Inhibition of the Monocarboxylate Transporter MCT1 by AZD3965 results in an increase in glycolysis in human tumor cell lines and xenografts. This is indicated by changes in the levels of specific glycolytic metabolites and in changes in glycolytic Enzyme kinetics. These drug-induced metabolic changes translate into an inhibition of tumor growth in vivo. Thus, we combined AZD3965 with fractionated radiation to treat small cell lung Cancer (SCLC) xenografts and showed that the combination provided a significantly greater therapeutic effect than the use of either modality alone. These results strongly support the notion of combining MCT1 inhibition with radiotherapy in the treatment of SCLC and other solid tumors.

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