TY  - JOUR
A1  - Wali, Vikram B.
A1  - Patwardhan, Gauri A.
A1  - Pelekanou, Vasiliki
A1  - Karn, Thomas
A1  - Cao, Jian
A1  - Ocana, Alberto
A1  - Yan, Qin
A1  - Nelson, Bryce
A1  - Hatzis, Christos
A1  - Pusztai, Lajos
T1  - Identification and validation of a novel biologics target in triple negative breast cancer
T2  - Scientific reports
N2  - The goal of this study was to identify a novel target for antibody-drug conjugate (ADC) development in triple negative breast cancer (TNBC), which has limited treatment options, using gene expression datasets and in vitro siRNA/CRISPR and in vivo functional assays. We analyzed 4467 breast cancers and identified GABRP as top expressed gene in TNBC with low expression in most normal tissues. GABRP protein was localized to cell membrane with broad range of receptors/cell (815–53,714) and expressed by nearly half of breast cancers tissues. GABRP gene knockdown inhibited TNBC cell growth and colony formation in vitro and growth of MDA-MB-468 xenografts in nude mice. Commercially available anti-GABRP antibody (5–100 μg/ml) or de novo generated Fabs (20 μg/ml) inhibited TNBC cell growth in vitro. The same antibody conjugated to mertansine (DM1) also showed significant anticancer activity at nanomolar concentrations. Our results indicate that GABRP is a potential novel therapeutic target for ADC development.
KW  - Breast cancer
KW  - Target identification
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/55103
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-551039
SN  - 2045-2322
N1  - Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 9
IS  - 1, Art. 14934
SP  - 1
EP  - 10
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -