Open AccessTargeting the PI 3K signaling pathway in KRAS mutant colon cancer
Author(s) -
Hong Suntaek,
Kim SoYoung,
Kim Hye Youn,
Kang Myunghee,
Jang Ho Hee,
Lee WonSuk
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.591
Subject(s) - cetuximab , kras , colorectal cancer , cancer research , mapk/erk pathway , cell growth , epidermal growth factor receptor , chemistry , mutant , kinase , cancer , biology , medicine , biochemistry , gene
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. BKM 120 targets phosphatidylinositide‐3‐kinase ( PIK 3 CA ), but it is unknown whether BKM 120 can reverse cetuximab resistance in KRAS mutant CRC . Human CRC cell lines with KRAS mutations ( DLD ‐1, HCT 116, and LoVo) were used to test the effect of cetuximab, BKM 120, and cetuximab plus BKM 120 on cell proliferation in vitro and in vivo. BKM 120 reduced cell proliferation in a concentration‐dependent manner in the LoVo ( PI 3 KCA wild type) as well as the HCT 116 and DLD 1 cells (that carry a PI 3 KCA mutation). BKM 120 only inhibited ERK phosphorylation in LoVo cells ( PIK 3 CA wild type), but not in DLD 1 or HCT 116 cells at a concentration of 1 μ mol/L. Treatment with cetuximab and BKM 120 significantly reduced the growth of xenograft tumors originating from KRAS mutant cells compared with cetuximab alone ( P = 0.034). BKM 120 may overcome cetuximab resistance in colon cancer cells with KRAS mutation.