Unknown

Dataset Information

0

Focal Adhesion Kinase Regulates the DNA Damage Response and Its Inhibition Radiosensitizes Mutant KRAS Lung Cancer.


ABSTRACT: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide due to the limited availability of effective therapeutic options. For instance, there are no effective strategies for NSCLCs that harbor mutant KRAS, the most commonly mutated oncogene in NSCLC. Thus, our purpose was to make progress toward the generation of a novel therapeutic strategy for NSCLC.We characterized the effects of suppressing focal adhesion kinase (FAK) by RNA interference (RNAi), CRISPR/CAS9 gene editing or pharmacologic approaches in NSCLC cells and in tumor xenografts. In addition, we tested the effects of suppressing FAK in association with ionizing radiation (IR), a standard-of-care treatment modality.FAK is a critical requirement of mutant KRAS NSCLC cells. With functional experiments, we also found that, in mutant KRAS NSCLC cells, FAK inhibition resulted in persistent DNA damage and susceptibility to exposure to IR. Accordingly, administration of IR to FAK-null tumor xenografts causes a profound antitumor effect in vivo CONCLUSIONS: FAK is a novel regulator of DNA damage repair in mutant KRAS NSCLC and its pharmacologic inhibition leads to radiosensitizing effects that could be beneficial in cancer therapy. Our results provide a framework for the rationale clinical testing of FAK inhibitors in NSCLC patients. Clin Cancer Res; 22(23); 5851-63. ©2016 AACR.

SUBMITTER: Tang KJ 

PROVIDER: S-EPMC5122471 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Focal Adhesion Kinase Regulates the DNA Damage Response and Its Inhibition Radiosensitizes Mutant KRAS Lung Cancer.

Tang Ke-Jing KJ   Constanzo Jerfiz D JD   Venkateswaran Niranjan N   Melegari Margherita M   Ilcheva Mariya M   Morales Julio C JC   Skoulidis Ferdinandos F   Heymach John V JV   Boothman David A DA   Scaglioni Pier Paolo PP  

Clinical cancer research : an official journal of the American Association for Cancer Research 20160524 23


<h4>Purpose</h4>Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide due to the limited availability of effective therapeutic options. For instance, there are no effective strategies for NSCLCs that harbor mutant KRAS, the most commonly mutated oncogene in NSCLC. Thus, our purpose was to make progress toward the generation of a novel therapeutic strategy for NSCLC.<h4>Experimental design</h4>We characterized the effects of suppressing focal adhesion kinase (  ...[more]

Similar Datasets

| S-EPMC3338902 | biostudies-literature
| S-EPMC6318062 | biostudies-literature
| S-EPMC6942685 | biostudies-literature
| S-EPMC4245398 | biostudies-literature
| S-EPMC10826079 | biostudies-literature
2013-09-17 | GSE43873 | GEO
2013-09-17 | E-GEOD-43873 | biostudies-arrayexpress
| S-EPMC5333956 | biostudies-literature
| S-EPMC5593625 | biostudies-literature
| S-EPMC3384409 | biostudies-literature