@article{e1cc9cdf2e0f40b09d1678a8ff10e8f9,
title = "SLC43A3 is a biomarker of sensitivity to the telomeric DNA damage mediator 6-thio-2′-deoxyguanosine",
abstract = "Cell membrane transporters facilitate the passage of nucleobases and nucleosides for nucleotide synthesis and metabolism, and are important for the delivery of nucleoside analogues used in anticancer drug therapy. Here, we investigated if cell membrane transporters are involved in the cellular uptake of the nucleoside analogue DNA damage mediator 6-thio-2′-deoxyguanosine (6-thio-dG). A large panel of non-small cell lung cancer (NSCLC) cell lines (73 of 77) were sensitive to 6-thio-dG; only four NSCLC lines were resistant to 6-thio-dG. When analyzed by microarray and RNA sequencing, the resistant NSCLC cell lines clustered together, providing a molecular signature for patients that may not respond to 6-thiodG. Significant downregulation of solute carrier family 43 A3 (SLC43A3), an equilibrative nucleobase transporter, was identified as a candidate in this molecular resistance signature. High levels of SLC43A3 mRNA predicted sensitivity to 6-thio-dG and therefore SLC43A3 could serve as a promising biomarker for 6-thio-dG sensitivity in patients with NSCLC. Significance: These findings identify a biomarker of resistance to the telomeric DNA damage mediator 6-thio-2′-deoxyguanosine.",
author = "Ilgen Mender and Kimberly Batten and Michael Peyton and Aishwarya Vemula and Crystal Cornelius and Luc Girard and Boning Gao and Minna, {John D.} and Shay, {Jerry W.}",
note = "Funding Information: This study was supported by NCI SPORE P50CA70907, the Johnson Foundation, and NIH grant C06RR30414. We acknowledge the assistance of UTSW Tissue Resource, a shared resource at the Simmons Comprehensive Cancer Center, which is supported in part by the NCI under award number 5P30CA142543 and UTSW Whole Brain Microscopy Facility in the Department of Neurology and Neurotherapeutics. The Whole Brain Microscopy Facility is supported by the Texas Institute for Brain Injury and Repair. We also acknowledge the CPRIT training grant, RP160157, and NCI T32 training grant CA124334 (I. Mender). J.W. Shay holds the distinguished Southland Financial Corporation Distinguished Chair in Geriatrics Research and is a founding scientist of Thio Therapeutics, Inc. (part of Maia Biotechnology). Funding Information: This study was supported by NCI SPORE P50CA70907, the Johnson Foundation, and NIH grant C06RR30414. We acknowledge the assistance of UTSW Tissue Resource, a shared resource at the Simmons Comprehensive Cancer Center, Funding Information: which is supported in part by the NCI under award number 5P30CA142543 and UTSW Whole Brain Microscopy Facility in the Department of Neurology and Neurotherapeutics. The Whole Brain Microscopy Facility is supported by the Texas Institute for Brain Injury and Repair. We also acknowledge the CPRIT training grant, RP160157, and NCI T32 training grant CA124334 (I. Mender). J.W. Shay holds the distinguished Southland Financial Corporation Distinguished Chair in Geriatrics Research and is a founding scientist of Thio Therapeutics, Inc. (part of Maia Biotechnology). Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",
year = "2020",
month = mar,
day = "1",
doi = "10.1158/0008-5472.CAN-19-2257",
language = "English (US)",
volume = "80",
pages = "929--936",
journal = "Cancer research",
issn = "0008-5472",
number = "5",
}