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Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer.

Publication ,  Journal Article
Roper, J; Sinnamon, MJ; Coffee, EM; Belmont, P; Keung, L; Georgeon-Richard, L; Wang, WV; Faber, AC; Yun, J; Yilmaz, ÖH; Bronson, RT; Hung, KE ...
Published in: Cancer Lett
June 1, 2014

PI3K inhibition in combination with other agents has not been studied in the context of PIK3CA wild-type, KRAS mutant cancer. In a screen of phospho-kinases, PI3K inhibition of KRAS mutant colorectal cancer cells activated the MAPK pathway. Combination PI3K/MEK inhibition with NVP-BKM120 and PD-0325901 induced tumor regression in a mouse model of PIK3CA wild-type, KRAS mutant colorectal cancer, which was mediated by inhibition of mTORC1, inhibition of MCL-1, and activation of BIM. These findings implicate mitochondrial-dependent apoptotic mechanisms as determinants for the efficacy of PI3K/MEK inhibition in the treatment of PIK3CA wild-type, KRAS mutant cancer.

Duke Scholars

Published In

Cancer Lett

DOI

EISSN

1872-7980

Publication Date

June 1, 2014

Volume

347

Issue

2

Start / End Page

204 / 211

Location

Ireland

Related Subject Headings

  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Oncology & Carcinogenesis
  • Mutation
  • Mice, Inbred C57BL
  • Mice
  • MAP Kinase Kinase Kinases
  • Humans
  • Genes, ras
  • Enzyme Inhibitors
 

Citation

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Roper, J., Sinnamon, M. J., Coffee, E. M., Belmont, P., Keung, L., Georgeon-Richard, L., … Hung, K. E. (2014). Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer. Cancer Lett, 347(2), 204–211. https://doi.org/10.1016/j.canlet.2014.02.018
Roper, Jatin, Mark J. Sinnamon, Erin M. Coffee, Peter Belmont, Lily Keung, Larissa Georgeon-Richard, Wei Vivian Wang, et al. “Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer.Cancer Lett 347, no. 2 (June 1, 2014): 204–11. https://doi.org/10.1016/j.canlet.2014.02.018.
Roper J, Sinnamon MJ, Coffee EM, Belmont P, Keung L, Georgeon-Richard L, et al. Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer. Cancer Lett. 2014 Jun 1;347(2):204–11.
Roper, Jatin, et al. “Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer.Cancer Lett, vol. 347, no. 2, June 2014, pp. 204–11. Pubmed, doi:10.1016/j.canlet.2014.02.018.
Roper J, Sinnamon MJ, Coffee EM, Belmont P, Keung L, Georgeon-Richard L, Wang WV, Faber AC, Yun J, Yilmaz ÖH, Bronson RT, Martin ES, Tsichlis PN, Hung KE. Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer. Cancer Lett. 2014 Jun 1;347(2):204–211.
Journal cover image

Published In

Cancer Lett

DOI

EISSN

1872-7980

Publication Date

June 1, 2014

Volume

347

Issue

2

Start / End Page

204 / 211

Location

Ireland

Related Subject Headings

  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Oncology & Carcinogenesis
  • Mutation
  • Mice, Inbred C57BL
  • Mice
  • MAP Kinase Kinase Kinases
  • Humans
  • Genes, ras
  • Enzyme Inhibitors