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Updated: Mar 28, 2026

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Targeting the PI3K signaling pathway in KRAS mutant colon cancer

Suntaek Hong1, SoYoung Kim2,3, Hye Youn Kim1

  • 1Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea.

Cancer Medicine
|December 31, 2015
PubMed

Insights

BKM120 may overcome cetuximab resistance in KRAS-mutant colorectal cancer (CRC). This study shows BKM120 plus cetuximab significantly reduced tumor growth in KRAS-mutant CRC models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • KRAS mutations in metastatic colorectal cancer (CRC) confer resistance to epidermal growth factor receptor (EGFR) inhibitors like cetuximab.
  • The efficacy of phosphatidylinositide-3-kinase (PI3K) inhibitors, such as BKM120, in overcoming this resistance is not well understood.

Purpose of the Study:

  • To investigate whether BKM120 can reverse cetuximab resistance in KRAS-mutant CRC.
  • To evaluate the combined effect of BKM120 and cetuximab on cancer cell proliferation and tumor growth.

Main Methods:

  • Utilized human CRC cell lines (DLD-1, HCT116, LoVo) harboring KRAS mutations.
  • Assessed the effects of cetuximab, BKM120, and their combination on cell proliferation in vitro and tumor growth in vivo (xenografts).
  • Monitored ERK phosphorylation to understand pathway inhibition.

Main Results:

  • BKM120 demonstrated dose-dependent inhibition of cell proliferation in both PIK3CA wild-type and mutant CRC cells.
  • BKM120 inhibited ERK phosphorylation only in PIK3CA wild-type cells at 1 μmol/L.
  • Combined cetuximab and BKM120 treatment significantly reduced xenograft tumor growth in KRAS-mutant CRC models compared to cetuximab alone (P=0.034).

Conclusions:

  • BKM120 shows potential in overcoming cetuximab resistance in colorectal cancer with KRAS mutations.
  • The combination therapy warrants further investigation for clinical application in KRAS-mutant CRC patients.
Keywords:
BKM120KRASPIK3CAcolon cancercombination therapy

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