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FAK-Copy-Gain Is a Predictive Marker for Sensitivity to FAK Inhibition in Breast Cancer

Title
FAK-Copy-Gain Is a Predictive Marker for Sensitivity to FAK Inhibition in Breast Cancer
Authors
Kim, Young-HoKim, Hyun-KyoungKim, Hee YeonGawk, HyeRanBae, Seung-HyunSim, Hye WonKang, Eun-KyungSeoh, Ju-YoungJang, HyoncholHong, Kyeong-Man
Ewha Authors
서주영
SCOPUS Author ID
서주영scopus
Issue Date
2019
Journal Title
CANCERS
ISSN
2072-6694JCR Link
Citation
CANCERS vol. 11, no. 9
Keywords
copy gain of FAKFAK inhibitorFAK-knockdowntarget therapybreast cancerAKT signaling
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS
Document Type
Article
Abstract
Background: Cancers with copy-gain drug-target genes are excellent candidates for targeted therapy. In order to search for new predictive marker genes, we investigated the correlation between sensitivity to targeted drugs and the copy gain of candidate target genes in NCI-60 cells. Methods: For eight candidate genes showing copy gains in NCI-60 cells identified in our previous study, sensitivity to corresponding target drugs was tested on cells showing copy gains of the candidate genes. Results: Breast cancer cells with Focal Adhesion Kinase (FAK)-copy-gain showed a significantly higher sensitivity to the target inhibitor, FAK inhibitor 14 (F14). In addition, treatment of F14 or FAK-knockdown showed a specific apoptotic effect only in breast cancer cells showing FAK-copy-gain. Expression-profiling analyses on inducible FAK shRNA-transfected cells showed that FAK/AKT signaling might be important to the apoptotic effect by target inhibition. An animal experiment employing a mouse xenograft model also showed a significant growth-inhibitory effect of F14 on breast cancer cells showing FAK-copy-gain, but not on those without FAK-copy-gain. Conclusion: FAK-copy-gain may be a predictive marker for FAK inhibition therapy in breast cancer.
DOI
10.3390/cancers11091288
Appears in Collections:
의과대학 > 의학과 > Journal papers
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