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FAK-Copy-Gain Is a Predictive Marker for Sensitivity to FAK Inhibition in Breast Cancer
- FAK-Copy-Gain Is a Predictive Marker for Sensitivity to FAK Inhibition in Breast Cancer
- Kim, Young-Ho; Kim, Hyun-Kyoung; Kim, Hee Yeon; Gawk, HyeRan; Bae, Seung-Hyun; Sim, Hye Won; Kang, Eun-Kyung; Seoh, Ju-Young; Jang, Hyonchol; Hong, Kyeong-Man
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- CANCERS vol. 11, no. 9
- copy gain of FAK; FAK inhibitor; FAK-knockdown; target therapy; breast cancer; AKT signaling
- SCIE; SCOPUS
- Document Type
- 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.
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