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- Title
Targeting the PI3K signaling pathway in KRAS mutant colon cancer.
- Authors
Hong, Suntaek; Kim, SoYoung; Kim, Hye Youn; Kang, Myunghee; Jang, Ho Hee; Lee, Won‐Suk
- Abstract
Metastatic colorectal cancer ( CRC) patients with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS) mutations are resistant to monoclonal antibody that targets the epidermal growth factor receptor such as cetuximab. BKM120 targets phosphatidylinositide-3-kinase ( PIK3 CA), but it is unknown whether BKM120 can reverse cetuximab resistance in KRAS mutant CRC. Human CRC cell lines with KRAS mutations ( DLD-1, HCT116, and LoVo) were used to test the effect of cetuximab, BKM120, and cetuximab plus BKM120 on cell proliferation in vitro and in vivo. BKM120 reduced cell proliferation in a concentration-dependent manner in the LoVo ( PI3 KCA wild type) as well as the HCT116 and DLD1 cells (that carry a PI3 KCA mutation). BKM120 only inhibited ERK phosphorylation in LoVo cells ( PIK3 CA wild type), but not in DLD1 or HCT116 cells at a concentration of 1 μmol/L. Treatment with cetuximab and BKM120 significantly reduced the growth of xenograft tumors originating from KRAS mutant cells compared with cetuximab alone ( P = 0.034). BKM120 may overcome cetuximab resistance in colon cancer cells with KRAS mutation.
- Subjects
COLON cancer; GENETIC mutation; CANCER cells; EPIDERMAL growth factor; CETUXIMAB
- Publication
Cancer Medicine, 2016, Vol 5, Issue 2, p248
- ISSN
2045-7634
- Publication type
Article
- DOI
10.1002/cam4.591