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

Becky M Bola; Amy Chadwick; Filippos Michopoulos; Kathryn G Blount; Brian A Telfer; Kaye Williams; Paul D Smith; Susan E Critchlow; Ian J Stratford

doi:10.1158/1535-7163.MCT-13-1091

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

Becky M Bola, Amy Chadwick, Filippos Michopoulos, Kathryn G Blount, Brian A Telfer, Kaye Williams, Paul D Smith, Susan E Critchlow, Ian J Stratford

Pharmacy

Research output: Contribution to journal › Article › peer-review

Abstract

Inhibition of the monocarboxylate transporter MCT1 by AZD3965 results in an increase in glycolysis in human tumour 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 tumour growth in vivo. Thus, we combined AZD3965 with fractionated radiation to treat 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 tumours.

Original language	English
Pages (from-to)	2805–16
Journal	Molecular Cancer Therapeutics
Volume	13
Issue number	12
DOIs	https://doi.org/10.1158/1535-7163.MCT-13-1091
Publication status	Published - 3 Oct 2014

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title = "Inhibition of Monocarboxylate transporter-1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport",

abstract = "Inhibition of the monocarboxylate transporter MCT1 by AZD3965 results in an increase in glycolysis in human tumour 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 tumour growth in vivo. Thus, we combined AZD3965 with fractionated radiation to treat 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 tumours.",

author = "Bola, {Becky M} and Amy Chadwick and Filippos Michopoulos and Blount, {Kathryn G} and Telfer, {Brian A} and Kaye Williams and Smith, {Paul D} and Critchlow, {Susan E} and Stratford, {Ian J}",

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doi = "10.1158/1535-7163.MCT-13-1091",

language = "English",

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T1 - Inhibition of Monocarboxylate transporter-1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport

AU - Bola, Becky M

AU - Chadwick, Amy

AU - Michopoulos, Filippos

AU - Blount, Kathryn G

AU - Telfer, Brian A

AU - Williams, Kaye

AU - Smith, Paul D

AU - Critchlow, Susan E

AU - Stratford, Ian J

PY - 2014/10/3

Y1 - 2014/10/3

N2 - Inhibition of the monocarboxylate transporter MCT1 by AZD3965 results in an increase in glycolysis in human tumour 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 tumour growth in vivo. Thus, we combined AZD3965 with fractionated radiation to treat 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 tumours.

AB - Inhibition of the monocarboxylate transporter MCT1 by AZD3965 results in an increase in glycolysis in human tumour 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 tumour growth in vivo. Thus, we combined AZD3965 with fractionated radiation to treat 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 tumours.

U2 - 10.1158/1535-7163.MCT-13-1091

DO - 10.1158/1535-7163.MCT-13-1091

M3 - Article

C2 - 25281618

VL - 13

SP - 2805

EP - 2816

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

IS - 12

ER -

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

Abstract

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