@article{25d35d0362b243889a7492d0150429be,
title = "An enolase inhibitor for the targeted treatment of ENO1-deleted cancers",
abstract = "Inhibiting glycolysis remains an aspirational approach for the treatment of cancer. We have previously identified a subset of cancers harbouring homozygous deletion of the glycolytic enzyme enolase (ENO1) that have exceptional sensitivity to inhibition of its redundant paralogue, ENO2, through a therapeutic strategy known as collateral lethality. Here, we show that a small-molecule enolase inhibitor, POMHEX, can selectively kill ENO1-deleted glioma cells at low-nanomolar concentrations and eradicate intracranial orthotopic ENO1-deleted tumours in mice at doses well-tolerated in non-human primates. Our data provide an in vivo proof of principle of the power of collateral lethality in precision oncology and demonstrate the utility of POMHEX for glycolysis inhibition with potential use across a range of therapeutic settings.",
author = "Lin, {Yu Hsi} and Nikunj Satani and Naima Hammoudi and Yan, {Victoria C.} and Yasaman Barekatain and Sunada Khadka and Ackroyd, {Jeffrey J.} and Georgiou, {Dimitra K.} and Pham, {Cong Dat} and Kenisha Arthur and David Maxwell and Zhenghong Peng and Leonard, {Paul G.} and Barbara Czako and Federica Pisaneschi and Pijus Mandal and Yuting Sun and Rafal Zielinski and Pando, {Susana Castro} and Xiaobo Wang and Theresa Tran and Quanyu Xu and Qi Wu and Yongying Jiang and Zhijun Kang and Asara, {John M.} and Waldemar Priebe and William Bornmann and Marszalek, {Joseph R.} and DePinho, {Ronald A.} and Muller, {Florian L.}",
note = "Funding Information: We thank S. Millward, S. Gammon, F. Lang, D. Pwinica-Worms, J. De Groot, P. Cserjesi, C. Halbrook, C. Lyssiotis and J. Huse for critical comments and suggestions. We thank H. Butterfield, L. Jacobs, A. Portal, P. Shresta, M. Washington and P. Suriyamongkol for technical assistance. We thank J. Holton and G. Meigs for their assistance with X-ray diffraction data collection. We thank K. Kalurachchi and J. McMurray for assistance with NMR. The UT M.D. Anderson Cancer Center NMR Core Facility is supported in part by the NCI Cancer Center Support Grant (CA16672). We thank M. Yuan and S. Breitkopf for help with the mass-spectrometry experiments. We thank Z. Jia for technical support with NHP experiments at CRL. We thank J. Long for help with statistical analysis and for critical reading. We thank K. Michel, C. Kingsley, V. Tran and the rest of the SAIF team for expert assistance with MRI imaging, and G. Rao, V. Henry, J. Gumin and F. Lang for GSC{\textquoteright}s and intracranial cell implantations. The Pharmaceutical Chemistry Facility and the Small Animal Imaging Facility at The UT M.D. Anderson Cancer Center were supported by the NIH/NCI Cancer Center Support Grant under award number P30CA016672. Financial support was provided by NIH CDP SPORE P50CA127001-07 (F.L.M.), NIH SPORE 2P50CA127001-11A1 (F.L.M.), ACS RSG-15-145-01-CDD (F.L.M.), NCCN YIA170032 (F.L.M. Young Investigator Award), The Andrew Sabin Family Foundation (F.L.M. Fellow award), The Dr. Marnie Rose Foundation (F.L.M.), The Uncle Kory Foundation (F.L.M.) and The University of Texas MD Anderson Cancer Center Institutional Research Grant (F.L.M.), CPRIT RP140612 (R.A.D.) and NIH R01 CA225955 (R.A.D). This work is dedicated to the memory of Dr. John Stuart McMurray, an expert in phosphonate prodrug synthesis, without whom this would not have been possible. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2020",
month = dec,
doi = "10.1038/s42255-020-00313-3",
language = "English (US)",
volume = "2",
pages = "1413--1426",
journal = "Nature Metabolism",
issn = "2522-5812",
publisher = "Springer Berlin",
number = "12",
}