Dual Inhibition of MEK and PI3K Pathway in KRAS and BRAF Mutated Colorectal Cancers
Abstract
:1. Introduction
2. Cross-Talk between MEK and PI3K Pathway
3. Pre-Clinical Data on Dual Targeted Inhibition with MEK
3.1. Combined Inhibition of MEK and mTOR
3.2. Combined MEK and PI3K Inhibition
3.3. Combined MEK and P13K/mTOR Inhibition
3.4. Combined MEK and AKT Inhibition
3.5. Combined Inhibition of MEK and IGFR
4. Clinical Trials on Dual Targeted Inhibition with MEK
Trial | MEK Inhibitor | PI3K Inhibitor | Phase | Population |
---|---|---|---|---|
NCT01363232 | MEK162 | BKM120 | Phase I | Patients with advanced solid cancers (colorectal cancer, triple-negative breast cancer, pancreatic cancer, and other cancers harboring KRAS, BRAF and NRAS mutations) |
NCT01392521 | BAY86-9766 | BAY80-6946 | Phase Ib | Patients with advanced solid cancers |
NCT01449058 | MEK162 | BYL719 | Phase II | Patients with advanced solid cancers (colorectal cancer, esophageal cancer, pancreatic cancer, non-small cell lung cancer, and other advanced solid tumors harboring RAS or BRAF mutations) |
Trial | MEK Inhibitor | PI3K/mTOR Inhibitor | Phase | Population |
NCT00996892 | GDC-0973 | Pictilisb (GDC-0941) | Phase I | Patients with advanced solid cancers |
NCT01337765 | MEK162 | BEZ235 | Phase 1 | Patients with advanced solid cancers (colorectal cancer, triple-negative breast cancer, pancreatic cancer, malignant melanoma, non-small cell lung cancer, and other cancers harboring KRAS, BRAF and NRAS mutation) |
NCT01390818 | Pimasertib (MSC1936369B) | SAR245409 | Phase 1 | Patients with advanced solid cancers (colorectal cancer, pancreatic cancer, thyroid cancer, non-small cell lung cancer, renal cancer, breast cancer, melanoma, ovarian cancer) and any cancer diagnosed with aberrations in one or more the following genes: PTEN, BRAF, KRAS, NRAS, PI3KCA, ErbB1, ErbB2) |
NCT01347866 | PD0325901 | PF-05212384 | Phase 1 | Patients with advanced solid cancers harboring KRAS or BRAF mutation and patients with KRAS mutation with no more than one prior systemic therapy regimen |
Trial | MEK Inhibitor | AKT Inhibitor | Phase | Population |
NCT01562275 | GDC-0973 | GDC-0068 | Phase 1 | Patients with locally advanced or metastatic solid tumors |
5. Conclusions
Author Contributions
Conflicts of Interest
References
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Temraz, S.; Mukherji, D.; Shamseddine, A. Dual Inhibition of MEK and PI3K Pathway in KRAS and BRAF Mutated Colorectal Cancers. Int. J. Mol. Sci. 2015, 16, 22976-22988. https://doi.org/10.3390/ijms160922976
Temraz S, Mukherji D, Shamseddine A. Dual Inhibition of MEK and PI3K Pathway in KRAS and BRAF Mutated Colorectal Cancers. International Journal of Molecular Sciences. 2015; 16(9):22976-22988. https://doi.org/10.3390/ijms160922976
Chicago/Turabian StyleTemraz, Sally, Deborah Mukherji, and Ali Shamseddine. 2015. "Dual Inhibition of MEK and PI3K Pathway in KRAS and BRAF Mutated Colorectal Cancers" International Journal of Molecular Sciences 16, no. 9: 22976-22988. https://doi.org/10.3390/ijms160922976