Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. Genetic mutations in the phosphatidylinositol-3 kinase (PI3K) and the mitogen activated protein kinase (MAPK) pathways are frequently implicated in CRC. Targeting the downstream substrate MEK in these mutated tumors stands out as a potential target in CRC. Several selective inhibitors of MEK have entered clinical trial evaluation; however, clinical activity with single MEK inhibitors has been rarely observed and acquired resistance seems to be inevitable. Amplification of the driving oncogene KRAS(13D), which increases signaling through the ERK1/2 pathway, upregulation of the noncanonical wingless/calcium signaling pathway (Wnt), and coexisting PIK3CA mutations have all been implicated with resistance against MEK inhibitor therapy in KRAS mutated CRC. The Wnt pathway and amplification of the oncogene have also been associated with resistance to MEK inhibitors in CRCs harboring BRAF mutations. Thus, dual targeted inhibition of MEK and PI3K pathway effectors (mTOR, PI3K, AKT, IGF-1R or PI3K/mTOR inhibitors) presents a potential strategy to overcome resistance to MEK inhibitor therapy. Many clinical trials are underway to evaluate multiple combinations of these pathway inhibitors in solid tumors.
机构:
Flinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, AustraliaFlinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, Australia
Sorich, M. J.
Wiese, M. D.
论文数: 0引用数: 0
h-index: 0
机构:
Univ S Australia, Sch Pharm & Med Sci, Adelaide, SA 5001, AustraliaFlinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, Australia
Wiese, M. D.
Rowland, A.
论文数: 0引用数: 0
h-index: 0
机构:
Flinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, AustraliaFlinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, Australia
Rowland, A.
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机构:
Kichenadasse, G.
McKinnon, R. A.
论文数: 0引用数: 0
h-index: 0
机构:
Flinders Univ S Australia, Sch Med, Flinders Ctr Innovat Canc, Adelaide, SA 5001, AustraliaFlinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, Australia
McKinnon, R. A.
Karapetis, C. S.
论文数: 0引用数: 0
h-index: 0
机构:
Flinders Univ S Australia, Sch Med, Flinders Ctr Innovat Canc, Adelaide, SA 5001, AustraliaFlinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, Australia
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Spreafico, Anna
Tentler, John J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Tentler, John J.
Pitts, Todd M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Pitts, Todd M.
Tan, Aik Choon
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Tan, Aik Choon
Gregory, Mark A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Dept Mol Biol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Gregory, Mark A.
Arcaroli, John J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Arcaroli, John J.
Klauck, Peter J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Klauck, Peter J.
McManus, Martine C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Dept Pathol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
McManus, Martine C.
Hansen, Ryan J.
论文数: 0引用数: 0
h-index: 0
机构:
Colorado State Univ, Dept Clin Sci, Ft Collins, CO 80523 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Hansen, Ryan J.
Kim, Jihye
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Kim, Jihye
Micel, Lindsey N.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USA
Childrens Hosp Colorado, Div Pediat Hematol Oncol, Aurora, CO USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Micel, Lindsey N.
Selby, Heather M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Selby, Heather M.
Newton, Timothy P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Newton, Timothy P.
McPhillips, Kelly L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
McPhillips, Kelly L.
Gustafson, Daniel L.
论文数: 0引用数: 0
h-index: 0
机构:
Colorado State Univ, Dept Clin Sci, Ft Collins, CO 80523 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Gustafson, Daniel L.
DeGregori, James V.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Dept Mol Biol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
DeGregori, James V.
Messersmith, Wells A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Messersmith, Wells A.
Winn, Robert A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Winn, Robert A.
Eckhardt, S. Gail
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Harvard Univ, Sch Med, Dept Med, Boston, MA USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Turke, Alexa B.
Song, Youngchul
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Song, Youngchul
Costa, Carlotta
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Costa, Carlotta
Cook, Rebecca
论文数: 0引用数: 0
h-index: 0
机构:
Vanderbilt Ingram Canc Ctr, Nashville, TN USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Cook, Rebecca
Arteaga, Carlos L.
论文数: 0引用数: 0
h-index: 0
机构:
Vanderbilt Ingram Canc Ctr, Nashville, TN USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Arteaga, Carlos L.
Asara, John M.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Med, Boston, MA USA
Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Asara, John M.
Engelman, Jeffrey A.
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Harvard Univ, Sch Med, Dept Med, Boston, MA USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
机构:
Pfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USAPfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USA
Wang, YL
Van Becelaere, K
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h-index: 0
机构:
Pfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USAPfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USA
Van Becelaere, K
Jiang, P
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h-index: 0
机构:
Pfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USAPfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USA
Jiang, P
Przybranowski, S
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h-index: 0
机构:
Pfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USAPfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USA
Przybranowski, S
Omer, C
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h-index: 0
机构:
Pfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USAPfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USA
Omer, C
Sebolt-Leopold, J
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Pfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USAPfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USA
机构:
Flinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, AustraliaFlinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, Australia
Sorich, M. J.
Wiese, M. D.
论文数: 0引用数: 0
h-index: 0
机构:
Univ S Australia, Sch Pharm & Med Sci, Adelaide, SA 5001, AustraliaFlinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, Australia
Wiese, M. D.
Rowland, A.
论文数: 0引用数: 0
h-index: 0
机构:
Flinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, AustraliaFlinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, Australia
Rowland, A.
论文数: 引用数:
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机构:
Kichenadasse, G.
McKinnon, R. A.
论文数: 0引用数: 0
h-index: 0
机构:
Flinders Univ S Australia, Sch Med, Flinders Ctr Innovat Canc, Adelaide, SA 5001, AustraliaFlinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, Australia
McKinnon, R. A.
Karapetis, C. S.
论文数: 0引用数: 0
h-index: 0
机构:
Flinders Univ S Australia, Sch Med, Flinders Ctr Innovat Canc, Adelaide, SA 5001, AustraliaFlinders Univ S Australia, Sch Med, Dept Clin Pharmacol, Adelaide, SA 5001, Australia
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Spreafico, Anna
Tentler, John J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Tentler, John J.
Pitts, Todd M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Pitts, Todd M.
Tan, Aik Choon
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Tan, Aik Choon
Gregory, Mark A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Dept Mol Biol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Gregory, Mark A.
Arcaroli, John J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Arcaroli, John J.
Klauck, Peter J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Klauck, Peter J.
McManus, Martine C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Dept Pathol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
McManus, Martine C.
Hansen, Ryan J.
论文数: 0引用数: 0
h-index: 0
机构:
Colorado State Univ, Dept Clin Sci, Ft Collins, CO 80523 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Hansen, Ryan J.
Kim, Jihye
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Kim, Jihye
Micel, Lindsey N.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USA
Childrens Hosp Colorado, Div Pediat Hematol Oncol, Aurora, CO USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Micel, Lindsey N.
Selby, Heather M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Selby, Heather M.
Newton, Timothy P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Newton, Timothy P.
McPhillips, Kelly L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
McPhillips, Kelly L.
Gustafson, Daniel L.
论文数: 0引用数: 0
h-index: 0
机构:
Colorado State Univ, Dept Clin Sci, Ft Collins, CO 80523 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Gustafson, Daniel L.
DeGregori, James V.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Dept Mol Biol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
DeGregori, James V.
Messersmith, Wells A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Messersmith, Wells A.
Winn, Robert A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
Winn, Robert A.
Eckhardt, S. Gail
论文数: 0引用数: 0
h-index: 0
机构:
Univ Colorado, Div Med Oncol, Aurora, CO 80045 USAUniv Colorado, Div Med Oncol, Aurora, CO 80045 USA
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Harvard Univ, Sch Med, Dept Med, Boston, MA USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Turke, Alexa B.
Song, Youngchul
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Song, Youngchul
Costa, Carlotta
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Costa, Carlotta
Cook, Rebecca
论文数: 0引用数: 0
h-index: 0
机构:
Vanderbilt Ingram Canc Ctr, Nashville, TN USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Cook, Rebecca
Arteaga, Carlos L.
论文数: 0引用数: 0
h-index: 0
机构:
Vanderbilt Ingram Canc Ctr, Nashville, TN USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Arteaga, Carlos L.
Asara, John M.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Med, Boston, MA USA
Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Asara, John M.
Engelman, Jeffrey A.
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
Harvard Univ, Sch Med, Dept Med, Boston, MA USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA
机构:
Pfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USAPfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USA
Wang, YL
Van Becelaere, K
论文数: 0引用数: 0
h-index: 0
机构:
Pfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USAPfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USA
Van Becelaere, K
Jiang, P
论文数: 0引用数: 0
h-index: 0
机构:
Pfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USAPfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USA
Jiang, P
Przybranowski, S
论文数: 0引用数: 0
h-index: 0
机构:
Pfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USAPfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USA
Przybranowski, S
Omer, C
论文数: 0引用数: 0
h-index: 0
机构:
Pfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USAPfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USA
Omer, C
Sebolt-Leopold, J
论文数: 0引用数: 0
h-index: 0
机构:
Pfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USAPfizer Global Res & Dev, Ann Arbor Labs, Mol Sci & Technol, Ann Arbor, MI 48105 USA