In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3454-3454
Abstract:
Lung cancer is the leading cause of cancer related mortality in the US of which more than 75% cases are that of non-small cell lung carcinoma (NSCLC). Mutations in the proto-oncogene KRAS have been linked with poor prognosis for NSCLC patients. In this study, we aimed at analyzing the relationship between specific KRAS mutations and NSCLC cell radiosensitivity and protein expression patterns. We analyzed 22 NSCLC cell lines and stratified them according to their KRAS status. Our results show that NSCLC cells harbouring G12C mutations are more sensitive to radiation compared to cells with other KRAS status (SF2 = 0.35 ± 0.16 for G12C vs. 0.63 ± 0.17 for other KRAS mutants vs 0.54 ± 0.15 for wt KRAS). Our protein expression data suggests that G12C mutants have reduced expression of DNA-repair proteins such as ATM, Rad 50, Ku 80 and XRCC1 (p & lt; 0.05) which may be responsible for their radiosensitive nature. Further we found that G12C mutant NSCLC cell lines have reduced expression of pAkt compared to cells with other KRAS status (p =0.009). This suggests that NSCLC cells harboring G12C mutation would be less susceptible to PI3K inhibition induced radio-sensitization. Our clonogenic assay results confirm our finding when 1-hour pretreatment with 5 µM LY294002 (PI3K inhibitor) sensitized H460 and A549 (non-G12C mutated NSCLC cells) but not H1792 and H23 (G12C mutant NSCLC). Our results strongly suggests that G12C KRAS mutant cells are radio-sensitive compared to NSCLC cells of other KRAS status and PI3K inhibitor therapy along with radiation could be beneficial for patients harboring non-G12C mutational KRAS status. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3454. doi:1538-7445.AM2012-3454
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-3454
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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